ETM Experimental and Therapeutic Medicine 1792-0981 1792-1015 D.A. Spandidos ETM-31-6-13174 10.3892/etm.2026.13174 Articles Dexmedetomidine alleviates acute lung injury in humans by modulating the JAK1-STAT3 axis DingXianchao ShiDaoming WangJieru CaiHonghua YanZhixin Department of Burns and Plastic Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China Correspondence to: Dr Xianchao Ding. Department of Burns and Plastic Surgery, Affiliated Hospital of Jiangsu University, 438 Jiefang Road, Zhenjiang, Jiangsu 212001, P.R. China robertding3324@126.com 062026 28042026 31 6 179 07 01 2026 31 03 2026 Copyright © 2026, Spandidos Publications 2026

The clinical efficacy of dexmedetomidine (Dex) in acute lung injury (ALI) and its related molecular mechanisms in human systems are poorly defined. In the present study the modulatory functions of Dex in human ALI were investigated, together with identification of the key molecular pathways involved. Human respiratory epithelial cell lines (A549 and BEAS2b) were cultured in vitro and categorized into four experimental groups: Untreated control (Con), Dex-treated, lipopolysaccharide (LPS)-treated, and both LPS + Dex-treated (LPS + Dex) groups. In BEAS-2B cells, inflammatory cytokine levels in the culture supernatant and cell viability were measured in all groups. In A549 cells, proliferative capacity and apoptosis rates were evaluated. The mRNA levels of caspase-3 and BCL-2, BAX within the BEAS-2B cells after LPS exposure were examined using reverse transcription-quantitative PCR. The levels of Janus kinase 1 (JAK1) and signal transduction and transcription activation 3 (STAT3) proteins, along with their phosphorylated forms in A549 cells, were analyzed via western blotting. Dex substantially suppressed LPS-mediated elevation of IL-1β, IL-6 and TNF-α. LPS-associated reductions in cell viability and proliferative activity were markedly attenuated following Dex treatment. It also lowered the LPS-induced increase in apoptotic cell populations. The upregulation of caspase-3 and BAX gene expression after LPS stimulation in BEAS-2B cells was decreased by Dex treatment. The downregulation of BCL-2 gene expression after LPS stimulation in BEAS-2B cells was alleviated by Dex treatment. Moreover, Dex suppressed LPS-induced stimulation of the JAK1/STAT3 signaling cascade, as evidenced by downregulation of phosphorylated (p-)STAT3 and p-JAK1 in the A549 cells. Dex showed a protective effect against human ALI in vitro by reducing inflammatory responses, maintaining epithelial cell viability and decreasing apoptosis rate of epithelial cell. Modulation of the JAK1/STAT3 signaling cascade plays a crucial role in mediating these effects.

 dexmedetomidine acute lung injury Janus kinase 1-signal transduction and transcription activation 3 signaling pathways Funding: No funding was received. Introduction

Acute lung injury (ALI) is a major global health burden with ~75,000 deaths each year (1). The features of ALI include an exaggerated inflammatory response and abnormally increased vessel permeability (2). Exaggerated inflammatory response is a result of neutrophil infiltration and macrophage polarization, which was characterized by excessive release of pro-inflammatory cytokines such as IL-1β, IL-6, or TNF-α. Pathogenesis of increased vessel permeability involves damage to the alveolar epithelial cells, dysfunction of the alveolar capillary barrier, and injury of the vascular endothelial cells (3). Apoptosis, a self-controlled cell death pathway, is vital in the process of ALI (4). Bcl-2 family members and caspase family members are involved in the regulation of apoptosis (5). In the absence of timely and effective intervention, ALI may progress to acute respiratory distress syndrome, a condition associated with markedly increased mortality. The development of ALI has been closely linked to excessive exposure to bacterial endotoxins, chemical injury, and immune system dysregulation (6). Therefore, treatment strategies for ALI primarily focus on suppressing uncontrolled inflammation. Drugs with potent anti-inflammatory effects, such as glucocorticoids, enhance clinical outcomes in ALI patients (7). As well as glucocorticoids, other compounds, such as daphnetin (8), corylin (9) and astaxanthin (10), have shown promise for treating ALI by targeting inflammatory pathways.

Dexmedetomidine (Dex) is a potent and specific agonist of α2-adrenergic receptors and has well-documented systemic anti-inflammatory effects (11). These effects protect multiple organs during septic conditions (12). Emerging evidence suggests that Dex can improve ALI (13); however, the molecular mechanisms behind this protective action are not fully understood and appear to involve multiple signaling pathways. In a study by Li et al (14), it was found that Dex reduced the sepsis-induced ALI by regulating macrophage phagocytic activity via the reactive oxygen species-a disintegrin and Metalloproteinase 10/AXL axis. Cui et al (15) reported that Dex reduces lipopolysaccharide (LPS)-induced ALI by inhibiting the Phosphoinositide 3-kinase/Akt/phosphorylated forkhead box-O transcription factor 1 axis. Han et al (16) also showed that Dex reduces ALI by suppressing TLR4/NF-κB signaling.

The Janus kinase 1 (JAK1) and signal transduction and transcription activation 3 (STAT3) cascade is crucial for modulating inflammatory and immune responses (17) and is critical in the development of cytokine storms (18). Hyperactivation of the JAK/STAT pathway has been shown to exacerbate ALI by promoting the excessive release of pro-inflammatory mediators (19), whereas suppression of this pathway attenuates lung injury (20). The JAK/STAT signaling cascade comprises membrane-associated JAK tyrosine kinases JAK1, 2, 3 and TYK2) and intracellular STAT transcription factors (STAT1, 4, 5a, 5b and 6) (21). JAK and STAT proteins both become functionally active after phosphorylation, enabling phosphorylated STAT molecules to dimerize and enter the nucleus, where they modulate the transcriptional activity of specific downstream genes. Previous studies suggested that the JAK1/STAT3 axis is involved in modulating ALI in mouse models (22,23). However, its function in actions of Dex in ALI remain unclear. The present investigation aimed to examine the function of the JAK1/STAT3 pathway in Dex-mediated protection against human ALI.

 Materials and methods <sec> <title>Chemicals and reagents

A549 and BEAS-2B cell lines were both obtained from HySigen Biosciences. LPS was obtained from Bioseth Biotechnology Co., Ltd. Dex was supplied by THIAI (Shanghai) Chemical Industry Development Co., Ltd. The CCK-8 assay kit was provided by Bebo Biotech. ELISA kits were purchased from Quanzhou Jiubang Biotechnology Co., Ltd. The reverse transcription-quantitative (RT-q)PCR reagent kit was from AidLab Biotechnologies Co Ltd. The BCA kit was from Beijing Solarbio Science & Technology Co., Ltd. A PAGE gel preparation kit was from Epizyme Biotechnology. Rabbit anti-human GAPDH antibody was from Affinity Biosciences. Rabbit anti-human primary antibodies against phosphorylated (p-)JAK1, JAK1, STAT3 and p-STAT3 were from Proteintech Group, Inc. Goat anti-rabbit secondary antibody was from Proteintech Group, Inc. A TUNEL apoptosis detection kit was from Wuhan Elabscience Biotechnology Co., Ltd.

 Experimental subjects and grouping

A549 cells were maintained in DMEM enriched with 1% penicillin-streptomycin and 10% newborn calf serum, while BEAS-2B cells were grown in RPMI 1640 with 10% newborn calf serum and 1% antibiotics (all Keygen BIO). Cells were subcultured every alternate day and experiments were conducted using third-passage cells (P3). The two cell lines were randomly assigned to four treatment conditions: Untreated control, Dex, LPS, and combined LPS + Dex. The control group was not treated. The Dex group was exposed to 10 µmol/l Dex (final concentration). The LPS group was exposed to LPS at 10 µg/ml. In the combined treatment group, the culture media contained both LPS (10 µg/ml) and Dex (10 µmol/l).

 Detection of inflammatory cytokines

BEAS-2B cells (1x105/well) were grown in six-well plates at 37˚C with 5% CO2. Culture supernatants from each treatment group were obtained, and the inflammatory cytokines were detected via ELISA) kits (cat. nos. QZ-10489, QZ10469, QZ10789) as directed. Standard curves were plotted using the provided recommendations, and cytokine levels in each group were calculated from these curves.

 CCK-8 assays

BEAS-2B cells (2x103/well) were grown in 96-well plates, after which 10 µl of CCK-8 reagent was introduced to the wells for a duration equal to 2 h. Absorbance values (450 nm) were obtained using a microplate reader at predetermined time points, and cell viability was determined.

 Colony formation assays

The proliferative ability of A549 cells was observed using colony formation assays. Cells from each treatment group were grown (1x103/well in 2.5 ml of medium) in six-well plates over 2 weeks, after which cells were fixed [4% paraformaldehyde (PFA)] at 4 ˚C for 15 min and stained (crystal violet) at 20˚C for 30 min. Visible colonies (diameter >1 mm) were counted and recorded for each well.

 Detection of cell apoptosis

Apoptosis in all cell lines was examined using TUNEL) assay. A549 cells (5x105/well in 2.5 ml medium) were grown in 6-well plates. Treated cells were fixed (4% PFA, 20 min), permeabilized (0.1% Triton X-100, 30 min room temperature) and cleaned (thrice) using PBS. TUNEL staining was performed as per the kit protocol. Cell nuclei were labelled using DAPI at 20˚C for 5 min, and apoptotic cells were labeled with the TdT enzyme at 37˚C for 30 min. All images (fluorescence field) were captured and analyzed using ImageJ (version 1.6.0, National Institutes of Health).

 Gene expression analysis

A549 cells (5x105/well in 2.5 ml medium) were grown in 6-well plates for 24 h, Then total content of RNA was isolated from A549 cells using TRIpure (Aidlab Biotechnologies Co., Ltd.), followed by RT to synthesize cDNA with TRUEscript RT MasterMix (Aidlab Biotechnologies Co., Ltd.). RT was performed at 42˚C for 15 min, followed by inactivation at 85˚C for 5 sec. Quantitative PCR was conducted on a QuantStudio 5 system (Thermo Fisher) using SYBR Green qPCR Mix (Aidlab Biotechnologies Co., Ltd.), with denaturation for 3 min at 94˚C, 40 cycles at 94˚C for a duration equal to 10 sec each and at 60˚C for a duration equal to 30 sec. Primer sequences were: β-actin Forward CGTTGACATCCGTAAAGACC, Reverse GCTAGGAGCCAGGGCAGTA; Bax Forward TGTTTTCTGACGGCAACTTCA), Reverse AGCCCATGATGGTTCTGATCA; Bcl-2 Forward CCTGTGGATGACTGAGTACCTGAAC, Reverse CAGCCAGGAGAAATCAAACAGA; caspase-3 Forward TGGATTATCCTGAGATGGGTTTATG), Reverse GCTGCATCGACATCTGTACCA).

β-actin represented the reference gene. Relative gene levels were noted via the 2−ΔΔCq technique (24). This experiment was repeated three times. Data were visualized in Excel (version 2016, Microsoft Corporation).

 Western blotting

BEAS-2B cells were grown until 90% confluence in six-well plates, and were then lysed with 100 µl RIPA lysis buffer (Solarbio Science & Technology Co., R0010) per well. Cell lysates were obtained, and the concentrations of the protein were determined via BCA assays. Proteins were electrophoresed on 10% SDS-PAGE at 150 V for 50 min, and blotted onto PVDF membranes at 250 mA for 90 min. Blots were kept in blocking solution (0.1% TBST with 5% BSA) at room temperature for a duration equal to 1 h, and then treated for 24 h at a temperature equal to 4˚C for 24 h with primary antibodies for GAPDH (Affinity, cat. no. AF7021, 1:3,000), JAK1 (Proteintech, 27284-1-AP, 1:3,000), p-JAK1 (FabGennix, PJAK1-140AP, 1:3,000), STAT3 (Proteintech, 10253-2-AP, 1:3,000) and p-STAT3 (FabGennix, PSTAT3-340AP, 1:3,000). Following cleaning with TBST, the membranes were kept with a goat anti-rabbit HRP-linked secondary antibody (Proteintech Group, Inc.; cat. no. SA00001-2, 1:1,000) at room temperature for a duration equal to 1 h. Bands were detected using an enhanced chemiluminescence reagent (MedChemExpress, HY-K2005) and ImageJ (version 1.6.0, National Institutes of Health) was used to quantify band intensities.

 Statistical analysis

Data were statistically analyzed using SAS software (version 9.2, SAS Institute Inc.), while GraphPad Prism (v9.0; Dotmatics) was used to generate graphs. Data that followed a normal distribution were depicted as mean ± standard deviation (SD). Differences among multiple experimental groups were evaluated using one way ANOVA before Bonferroni post hoc tests. P<0.05 was considered to indicate a statistically significant difference.

 Results <sec> <title>Dex suppresses LPS-induced inflammation in BEAS-2B cells

Levels of inflammatory mediators in culture supernatants were initially quantified across all experimental groups. Exposure to Dex alone did not markedly alter IL-1β, IL-6, or TNF-α levels relative to the control condition (P>0.05). By comparison, LPS induction remarkably upregulated the levels of these pro-inflammatory factors (P<0.01). Co-treatment with Dex substantially reduced the LPS-induced inflammatory response, as shown by lower cytokine levels (P<0.05; Fig. 1).

 Effect of Dex against LPS-induced suppression of BEAS-2B cell viability

Cell viability of BEAS-2B cells was evaluated at different time points after treatment. At 24 h post-treatment, no substantial differences were found in all four groups. At 48 h, a marked reduction in cell viability was found in the LPS-treated cells relative to the controls (P<0.05). This reduction was alleviated in the group receiving combined LPS and Dex treatment, with viability levels not considerably different from the control (P>0.05). At 72 h, LPS exposure continued to reduce cell viability substantially relative to the control (P<0.01). Although Dex attenuated this inhibitory effect, cell viability in the combined treatment group remained considerably less than in the controls (P<0.05; Fig. 2).

 Dexmedetomidine attenuates LPS-induced inhibition of A549 cell propagation

The proliferative ability of A549 cells was evaluated using a colony formation assay. No substantial variances in colony numbers were detected Dex-exposed and control cells (P>0.05). LPS exposure resulted in a significant decrease in colony formation relative to the control (P<0.05). Co-administration of Dex partly reversed the inhibitory effect of LPS. Colony counts in the Dex + LPS treatment group increased compared with following LPS exposure (P<0.05; Fig. 3).

 Dex decreases LPS-induced apoptosis in A549 cells

Apoptosis is crucial to the development of ALI, and modulating apoptotic activity can substantially influence disease severity. The apoptosis rates of A549 cells under different treatment conditions are illustrated in Fig. 4. LPS stimulation substantially accelerated the number of apoptotic cells relative to the control (P<0.05). Dex treatment considerably reduced the LPS-induced rise in apoptosis (P<0.05).

 Dexmedetomidine modulates apoptosis-related gene levels in LPS-stimulated A549 cells

The effects of Dex on apoptosis were assessed by measuring BAX, BCL-2, and caspase-3 levels. As shown in Fig. 5, Dex exposure did not change the levels of these genes relative to the controls (P>0.05), although LPS significantly upregulated BAX and caspase-3 expression while markedly downregulating BCL-2 (P<0.01). Co-treatment with Dex considerably attenuated these LPS-induced changes, decreasing the upregulation of BAX and caspase-3 and partially restoring BCL-2 levels (P<0.05).

 Dexmedetomidine inhibits the stimulation of the JAK1/STAT3 signaling in LPS-treated BEAS-2B cells

Stimulation of the JAK1/STAT3 axis is characterized by increased JAK1 and STAT3 phosphorylation (25). The western blotting results of p-JAK1, JAK1, STAT3, and p-STAT3 are shown in Fig. 6. Treatment with Dex alone did not considerably change the expression of these proteins relative to the control. Similarly, total JAK1 and STAT3 levels remained unchanged after LPS stimulation. However, LPS exposure substantially enhanced p-JAK1 and p-STAT3 expression (P<0.01), indicating pathway activation. In the group treated with both LPS and Dex, the JAK1, p-JAK1, and STAT3 levels did not differ considerably from those in the control, whereas p-STAT3 levels remained elevated (P<0.05). Importantly, the level of p-STAT3 upregulation was substantially less than that of the LPS-only group, suggesting that Dex partially inhibited the stimulation of the JAK1/STAT3 pathway.

 Discussion

As aforementioned, ALI is pathologically characterized by an uncontrolled and excessive inflammatory response (26). Therefore, inflammation indicators within the respiratory system are widely accepted as reliable markers for ALI severity. The current in vitro study showed that Dex attenuated inflammatory responses and apoptosis in two human respiratory epithelial cell lines, involving the JAK1/STAT3 signaling cascade. Although animal models are often used to study ALI, they do not fully mimic the pathological processes observed in humans. Due to the ethical and practical limitations of in vivo human experiments, the present study used human respiratory epithelial cell lines for an improved simulation of human disease conditions.

LPS from the cell walls of Gram-negative bacteria causes acute lung inflammation in humans (27). Exposure of A549 and BEAS-2B cells to LPS was therefore used to simulate the pathological features of human ALI. Pro-inflammatory mediators are key factors that markedly aggravate lung injury (28) and their levels serve as indicators of the severity of the inflammatory response. The elevation of these cytokines following LPS stimulation and their decrease with Dex treatment suggest a potent anti-inflammatory effect of Dex in human ALI. The number of α2-adrenergic receptors may vary between these two kinds of airway epithelial cells, but the protective effects of Dex can be observed in both cells. It was thus hypothesized that a canonical signal pathway, such as the JAK/STAT pathway, may be the underlying mechanism.

Apoptosis is crucially involved in the progression of ALI (29), although apoptotic responses differ among different cell types involved in lung injury (30). Increased apoptosis of inflammatory cells, such as neutrophils and macrophages, may aid in resolving inflammation and promoting recovery (31). By comparison, excessive apoptosis of respiratory epithelial cells disrupts alveolar and bronchial barrier integrity, resulting in increased alveolar protein-rich fluid leakage and exacerbation of lung injury (32). Suppression of epithelial cell apoptosis has been shown to improve LPS-induced ALI (33). Key mediators of apoptosis, such as Bcl-2, Bax, and caspase-3, are commonly used to evaluate apoptotic activity (34). Among these, Bcl-2 acts as an anti-apoptotic protein, while Bax and caspase-3 promote apoptotic processes (35). The present findings revealed that Dex attenuated LPS-induced elevation of Bax and caspase-3 and counteracted the LPS-associated reduction in Bcl-2. These results indicated that Dex efficiently inhibited LPS-induced apoptosis in epithelial cells. Consistent with these observations, Huang et al (36) reported that nerelimomab alleviates ALI by inhibiting apoptosis in A549 cells, and that modulating apoptosis in BEAS-2B cells has also been shown to markedly improve ALI outcomes (37). The inhibitory influence of Dex on apoptosis within both the BEAS-2B and the A549 cells further support its potential therapeutic role in human ALI.

The JAK1/STAT3 axis is known to be linked to ALI onset. Stimulation of JAK1 induces phosphorylation of STAT3, which enhances the transcription of genes involved in inflammation (38). Pharmacological inhibition of JAK1 is commonly used to treat inflammatory and immune-mediated disorders (39) and has also shown efficacy in viral pneumonia (40). In a study by Joshi et al (41), it was found that rapalol alleviated ALI by blocking JAK1 activation. Consistent with these findings, the present study revealed that Dex substantially reduced LPS-induced JAK1 phosphorylation, thereby attenuating inflammatory amplification and protecting against lung injury in human cell models. Phosphorylated STAT3 has been shown to exacerbate inflammatory responses by promoting the recruitment of inflammatory cells (17), an effect related to increased neutrophil extracellular trap formation during sepsis (42). By upregulating pro-inflammatory cytokines in lung epithelial cells, p-STAT3 leads to increased alveolar-capillary permeability (43). Kubra and Barabutis (44) reported that activation of STAT3 potentiates ALI by damaging the endothelial cells. Moreover, STAT3 activation supports M1 macrophage polarization, which further boosts inflammation in ALI (45). Therefore, inhibiting STAT3 has been reported to provide substantial protection against ALI (46). In line with these findings, Dex treatment substantially decreased STAT3 phosphorylation following LPS exposure, thus suppressing excessive inflammatory signaling. Unlike p-JAK1, the level of p-STAT3 did not return to normal under the combined treatment of LPS and Dex in the present study. This phenomenon indicated that STAT3 was not only activated by JAK1, but other upstream regulatory proteins, such as IL-6, also play a certain role (47).

Therapeutic agents exert protective effects against ALI through modulation of the JAK1/STAT3 pathway. Li et al (48) demonstrated that HHC alleviates ALI by regulating JAK1/STAT3 signaling, while Yin et al (49) reported that Zuojin Fang reduces ALI severity by downregulating this pathway. Zhang et al (50) showed that Dex alleviates ALI in mice by inhibiting JAK1/STAT3 signaling. The current findings extended these observations by demonstrating that Dex also exerts protective effects against ALI in human-derived cell models by modulating the JAK1/STAT3 signaling axis.

Despite these findings, the present study had several limitations. First, the study focused solely on the JAK1/STAT3 pathway and the potential involvement of other signaling pathways in Dex-mediated protection remains to be examined. Second, the exact mechanistic relationship between JAK1/STAT3 inhibition and the observed regulation of inflammatory and apoptotic responses has not been fully explored, necessitating further in-depth research. Third, the experiment model was an epithelial-only model, while the ALI pathology involves alveolar-capillary failure, neutrophil infiltration, and endothelial injury. More research should be performed to clarify the mechanism of Dex in ALI.

 Acknowledgements

Not applicable.

 Availability of data and materials

The data generated in the present study may be requested from the corresponding author.

 Authors' contributions

XD contributed to study conception and design. The manuscript was drafted by XD and revised by ZY. Data collection was performed by DS and JW. DS and JW confirm the authenticity of all the raw data. Data analysis were performed by HC. All authors have read and approved the final manuscript.

 Ethics approval and consent to participate

Not applicable.

 Patient consent for publication

Not applicable.

 Competing interests

The authors declare that they have no competing interests.

 References YadavHThompsonBTGajicOFifty years of research in ARDS. Is acute respiratory distress syndrome a preventable disease?Am J Respir Crit Care Med19572573620172804098710.1164/rccm.201609-1767CI YangXLiJMaYDongXQuJLiangFLiuJCurcumin-mediated enhancement of lung barrier function in rats with high-altitude-associated acute lung injury via inhibition of inflammatory responseRespir Res2535420243934226410.1186/s12931-024-02975-z ZhangLLiHLiDDaiQUnraveling the synergy of inflammation and apoptosis in sepsis-induced acute lung injury: Insights and therapeutic perspectives (review)Mol Med Rep333120264120101010.3892/mmr.2025.13741 DingZLMaYCLiuCMLuXWangRRTangMMHuaDXZhengLZhaoHFuL1-Nitropyrene induces acute lung injury via SYVN1/Caspase-11-mediated apoptosis and pyroptosis in pulmonary epithelial cellsFront Pharmacol17172359320264173755610.3389/fphar.2026.1723593 WuJYeJKongWZhangSZhengYProgrammed cell death pathways in hearing loss: A review of apoptosis, autophagy and programmed necrosisCell Prolif53e1291520203304787010.1111/cpr.12915 LongMEMallampalliRKHorowitzJCPathogenesis of pneumonia and acute lung injuryClin Sci (Lond)13674776920223562112410.1042/CS20210879 GuoHGuanJWuXWeiYZhaoJZhouYLiFPangHBPeptide-guided delivery improves the therapeutic efficacy and safety of glucocorticoid drugs for treating acute lung injuryMol Ther3187588920233660914510.1016/j.ymthe.2023.01.003 YangSSongYWangQLiuYWuZDuanXZhangYBiXGengYChenSZhuCDaphnetin ameliorates acute lung injury in mice with severe acute pancreatitis by inhibiting the JAK2-STAT3 pathwaySci Rep111149120213407516010.1038/s41598-021-91008-6 ChenICWangSCChenYTTsengHHLiuPLLinTCWuHEChenYRTsengYHHsuJHCorylin ameliorates LPS-induced acute lung injury via suppressing the MAPKs and IL-6/STAT3 signaling pathwaysPharmaceuticals (Basel)14104620213468127010.3390/ph14101046 ZhuLWuHMaZDongDYangZTianJAstaxanthin ameliorates lipopolysaccharide-induced acute lung injury via inhibition of inflammatory reactions and modulation of the SOCS3/JAK2/STAT3 signaling pathways in miceFood Funct13116381165120223627842010.1039/d2fo02182j WangKWuMXuJWuCZhangBWangGMaDEffects of dexmedetomidine on perioperative stress, inflammation, and immune function: Systematic review and meta-analysisBr J Anaesth12377779420193166834710.1016/j.bja.2019.07.027 ZhangQHuangYGongCTangYXiongJWangDLiuXDexmedetomidine attenuates inflammation and organ injury partially by upregulating Nur77 in sepsisImmun Inflamm Dis11e88320233738227310.1002/iid3.883 ShiJYuTSongKDuSHeSHuXLiXLiHDongSZhangYDexmedetomidine ameliorates endotoxin-induced acute lung injury in vivo and in vitro by preserving mitochondrial dynamic equilibrium through the HIF-1a/HO-1 signaling pathwayRedox Biol4110195420213377447410.1016/j.redox.2021.101954 LiFBaiYGuanZJiXZhanXGaoYZhongWRaoZDexmedetomidine attenuates sepsis-associated acute lung injury by regulating macrophage efferocytosis through the ROS/ADAM10/AXL pathwayInt Immunopharmacol14211283220243936281610.1016/j.intimp.2024.112832 CuiHZhangQDexmedetomidine ameliorates lipopolysaccharide-induced acute lung injury by inhibiting the PI3K/Akt/FoxO1 signaling pathwayJ Anesth3539440420213382130010.1007/s00540-021-02909-9 HanJLiuXWangLDexmedetomidine protects against acute lung injury in mice via the DUSP1/MAPK/NF-κB axis by inhibiting miR-152-3p. Pulm Pharmacol The: 102131, 2022 (Epub ahead of print). XinPXuXDengCLiuSWangYZhouXMaHWeiDSunSThe role of JAK/STAT signaling pathway and its inhibitors in diseasesInt Immunopharmacol8010621020203197242510.1016/j.intimp.2020.106210 KeenanCAlbeituniSNicholsKEHinesMJAK inhibitors in cytokine storm syndromesAdv Exp Med Biol144858360020243911784110.1007/978-3-031-59815-9_39 Al-AniBShamsEldeenAMKamarSSHaidaraMAAl-HashemFAlshahraniMYAl-HakamiAMKaderDHAMaaroufALipopolysaccharide induces acute lung injury and alveolar haemorrhage in association with the cytokine storm, coagulopathy and AT1R/JAK/STAT augmentation in a rat model that mimics moderate and severe Covid-19 pathologyClin Exp Pharmacol Physiol4948349120223506691210.1111/1440-1681.13620 SongZZhaoXGaoYLiuMHouMJinHCuiYRecombinant human brain natriuretic peptide ameliorates trauma-induced acute lung injury via inhibiting JAK/STAT signaling pathway in ratsJ Trauma Acute Care Surg7898098720152590941910.1097/TA.0000000000000602 XueCYaoQGuXShiQYuanXChuQBaoZLuJLiLEvolving cognition of the JAK-STAT signaling pathway: Autoimmune disorders and cancerSignal Transduct Target Ther820420233720833510.1038/s41392-023-01468-7 XuFWangSWangYHuLZhuLInhibition of gp130 alleviates LPS-induced lung injury by attenuating apoptosis and inflammation through JAK1/STAT3 signaling pathwayInflamm Res7249350720233661734210.1007/s00011-022-01686-9 ZhouJRLiaoYCaoLQMaRHeYLiNZhuDPZhaoXSHuangXJSunYQInterleukin 6 is significantly increased in severe pneumonia after allo-hematopoietic stem cell transplantation and might induce lung injury via IL-6/sIL-6R/JAK1/STAT3 pathwayJ Infect Dis23211312620253982890810.1093/infdis/jiaf041 LivakKJSchmittgenTDAnalysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) methodMethods2540240820011184660910.1006/meth.2001.1262 LinKCChangTMSunYSLinYRTangCHLiuJFCXCL8 drives MMP1 upregulation and promotes metastatic progression in oral cancer through CXCR1/2-mediated JAK1/STAT3 activationInt J Biol Sci222285230120264180023810.7150/ijbs.115990 ShanMZhangSLuoZDengSRanLZhouQWanHYeJQianCFanXItaconate promotes inflammatory responses in tissue-resident alveolar macrophages and exacerbates acute lung injuryCell Metab3717501765.e720254052731610.1016/j.cmet.2025.05.012 ZouXLiuCHuangZXiangSLiKYuanYHaoYZhouFInhibition of STEAP1 ameliorates inflammation and ferroptosis of acute lung injury caused by sepsis in LPS-induced human pulmonary microvascular endothelial cellsMol Biol Rep505667567420233720932710.1007/s11033-023-08403-7 TuYLiXFuYChenYFangHLiYGuYZhangJIsocorydine ameliorates IL-6 expression in bone marrow-derived macrophages and acute lung injury induced by lipopolysaccharideInt J Mol Sci24462920233690206010.3390/ijms24054629 JiaJYuanYHeYWastiBDuanWChenZLiDSunWZengQMaLInhibition of METTL3 alleviated LPS-induced alveolar epithelial cell apoptosis and acute lung injury via restoring neprilysin expressionLife Sci33312214820233780516610.1016/j.lfs.2023.122148 WangJFWangYPXieJZhaoZZGuptaSGuoYJiaSHParodoJMarshallJCDengXMUpregulated PD-L1 delays human neutrophil apoptosis and promotes lung injury in an experimental mouse model of sepsisBlood13880681020213447323010.1182/blood.2020009417 KurdowskaAKFlorenceJMPromoting neutrophil apoptosis to treat acute lung injuryAm J Respir Crit Care Med20039940020193104640610.1164/rccm.201903-0707LE LiXJamalMGuoPJinZZhengFSongXZhanJWuHIrisin alleviates pulmonary epithelial barrier dysfunction in sepsis-induced acute lung injury via activation of AMPK/SIRT1 pathwaysBiomed Pharmacother11810936320193154527710.1016/j.biopha.2019.109363 LiuLYuanYZhouYYaoLLiJChenFThe transcription factor KLF14 attenuates LPS-induced acute lung injury by ameliorating apoptosis of alveolar epithelial cells in miceMol Immunol152677720223627966010.1016/j.molimm.2022.10.002 ZhouXWangMSunMYaoNHSPB8 attenuates lipopolysaccharide-mediated acute lung injury in A549 cells by activating mitophagyMol Med Rep3017120243905496610.3892/mmr.2024.13295 LiJChenQHeXAlamANingJYiBLuKGuJDexmedetomidine attenuates lung apoptosis induced by renal ischemia-reperfusion injury through α2AR/PI3K/Akt pathwayJ Transl Med167820182956670610.1186/s12967-018-1455-1 HuangLDuBCuiXZhaoHFengYXuZLongJYuanJYouFNerelimomab alleviates capsaicin-induced acute lung injury by inhibiting TNF signaling and apoptosisPharmaceuticals (Basel)17169420243977053610.3390/ph17121694 YangJChenXSIRT6 attenuates LPS-induced inflammation and apoptosis of lung epithelial cells in acute lung injury through ACE2/STAT3/PIM1 signalingImmun Inflamm Dis11e80920233698824310.1002/iid3.809 SimsNAThe JAK1/STAT3/SOCS3 axis in bone development, physiology, and pathologyExp Mol Med521185119720203278865510.1038/s12276-020-0445-6 TravesPGMurrayBCampigottoFGalienRMengADi PaoloJAJAK selectivity and the implications for clinical inhibition of pharmacodynamic cytokine signalling by filgotinib, upadacitinib, tofacitinib and baricitinibAnn Rheum Dis8086587520213374155610.1136/annrheumdis-2020-219012 RECOVERY Collaborative GroupBaricitinib in patients admitted to hospital with COVID-19 (RECOVERY): A randomised, controlled, open-label, platform trial and updated meta-analysisLancet40035936820223590856910.1016/S0140-6736(22)01109-6 JoshiKSinghVChatterjeeSKhandelwalPNairRQureshiSSiddhSNuniaVAssessment of lapachol's anti-inflammatory effectiveness in mitigating sepsis-induced acute lung injuryFitoterapia18010629820253956195110.1016/j.fitote.2024.106298 ZhangZZhuQWangSShiCEpigallocatechin-3-gallate inhibits the formation of neutrophil extracellular traps and suppresses the migration and invasion of colon cancer cells by regulating STAT3/CXCL8 pathwayMol Cell Biochem47888789820233611223810.1007/s11010-022-04550-w LiWLiuQXiongWZhongXTianLDecoding STAT3: A new frontier in understanding and treating hyperoxic lung injuryFront Immunol16165782320254096974710.3389/fimmu.2025.1657823 KubraKTBarabutisNCeapin-A7 potentiates lipopolysaccharide-induced endothelial injuryJ Biochem Mol Toxicol37e2346020233743195810.1002/jbt.23460 ZhuoYLiDCuiLLiCZhangSZhangQZhangLWangXYangLTreatment with 3,4-dihydroxyphenylethyl alcohol glycoside ameliorates sepsis-induced ALI in mice by reducing inflammation and regulating M1 polarizationBiomed Pharmacother11610901220193114610710.1016/j.biopha.2019.109012 YangSZhouSWangWCaoLXueTXuJLvKHuangMA novel STAT3 CCD inhibitor for suppressing macrophage activation and lipopolysaccharide-induced acute lung injuryInt Immunopharmacol14311352320243947656310.1016/j.intimp.2024.113523 XuSDengKQLuCFuXZhuQWanSZhangLHuangYNieLCaiHInterleukin-6 classic and trans-signaling utilize glucose metabolism reprogramming to achieve anti- or pro-inflammatory effectsMetabolism15515583220243843810610.1016/j.metabol.2024.155832 LiRLiangQYangQDaiWXiaoYPanHZhangZLiuLLiXHexahydrocurcumin from Zingiberis rhizoma attenuates lipopolysaccharide-induced acute pneumonia through JAK1/STAT3 signaling pathwayPhytomedicine12215514120243783789810.1016/j.phymed.2023.155141 YinJYuZHouCPengYXiaoJJiangJProtective effect of zuojin fang on lung injury induced by sepsis through downregulating the JAK1/STAT3 signaling pathwayBiomed Res Int2021141963120213350601010.1155/2021/1419631 ZhangZMLiLZLiKHAnCYLiYLLiLWuGYThe effects of dexmedetomidine administered at various times on acute lung injury in ratsEur Rev Med Pharmacol Sci252093209820213366082210.26355/eurrev_202102_25114

Dex suppresses LPS-induced inflammation in BEAS-2B cells. (A) IL-1β, (B) IL-6, and (C) TNF-α. Data are expressed as mean ± SD (n=3). *P<0.05, **P<0.01. Dex dexmedetomidine; LPS, lipopolysaccharide.

Influence of Dex on cell viability after LPS exposure. Cell viability of BEAS-2B cells was assessed at different time points under different treatment conditions. Data are expressed as mean ± SD (n=4). *P<0.05, **P<0.01. Dex dexmedetomidine; LPS, lipopolysaccharide.

Dex attenuates inhibition of A549 cell propagation induced by LPS. (A) Representative images of colony formation assays under different treatment conditions. (B) Quantification of colony numbers. Data are expressed as mean ± SD (n=3). *P<0.05, **P<0.01. Dex dexmedetomidine; LPS, lipopolysaccharide.

Dex reduces apoptosis induced by LPS in A549 cells. (A) TUNEL staining of A549 cells following different treatments (scale bar, 100 µm). (B) Quantification of apoptotic cell rates in all groups. Data are expressed as mean ± SD (n=3). **P<0.01, ***P<0.001. Dex dexmedetomidine; LPS, lipopolysaccharide.

Dex modulates apoptosis-related gene level in LPS-stimulated A549 cells. #P<0.05 vs. LPS group, **P<0.01 vs. Control. Dex dexmedetomidine; LPS, lipopolysaccharide.

Dex modulates apoptosis-related gene level in LPS-stimulated A549 cells. (A) Western blotting images of JAK1, p-JAK1, and GAPDH. (B) Densitometric analysis of relative protein expression levels. (C) Western blotting images of STAT3, p-STAT3, and GAPDH. (D) Quantification of relative STAT3 and p-STAT3 levels. Data are mean ± SD. *P<0.05, **P<0.01. Dex dexmedetomidine; LPS, lipopolysaccharide; JAK1, Janus kinase 1; p-, phosphorylated; STAT3, signal transduction and transcription activation 3.