Protective effect of taurine on sepsis‑induced lung injury via inhibiting the p38/MAPK signaling pathway

Chen,Jiao; Xue,Xiang; Cai,Jianqin; Jia,Ling; Sun,Baodi; Zhao,Wei

doi:10.3892/mmr.2021.12292

Protective effect of taurine on sepsis‑induced lung injury via inhibiting the p38/MAPK signaling pathway

Authors:
- Jiao Chen
- Xiang Xue
- Jianqin Cai
- Ling Jia
- Baodi Sun
- Wei Zhao
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Affiliations: Department of Critical Care Medicine, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu 211100, P.R. China, Department of Emergency Medicine, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu 211100, P.R. China
Published online on: July 14, 2021 https://doi.org/10.3892/mmr.2021.12292
Article Number: 653
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Sepsis, a leading cause of acute lung injury (ALI), is characterized by an overwhelming systemic inflammatory response and widespread organ injury, particularly in the lungs. Taurine, an intracellular free amino acid, has been used for the treatment of various diseases, including lung injury; however, the underlying mechanisms are unclear. The present study aimed to investigate the protective effect of taurine on septic ALI and the underlying mechanism. A septic ALI model was established by performing cecal ligation and puncture (CLP) surgery on Sprague Dawley rats. Following successful model establishment, rats were treated with taurine. The results of hematoxylin and eosin, respiratory function detection, malondialdehyde level and superoxide dismutase activity determination and ELSIA demonstrated that taurine significantly alleviated lung injury, restored respiratory function, reduced oxidation and decreased the concentrations of inflammatory factors in CLP‑induced septic ALI model rats. In addition, compared with that in the ALI group, western blotting results indicated that taurine ameliorated lung epithelial injury by significantly increasing the expression levels of lung epithelial markers, E‑cadherin and occludin. The western blotting results demonstrated that, compared with the control group, the p38/MAPK and NF‑κB signaling pathways were significantly activated in CLP‑induced septic ALI model rats, but taurine significantly suppressed ALI‑mediated signaling pathway activation. To investigate the mechanism underlying taurine in the treatment of septic ALI, CLP‑induced septic ALI model rats were treated with an antagonist of the p38/MAPK signaling pathway (SB203580). The effects of SB203580 on CLP‑induced septic ALI model rats were similar to those of taurine. SB203580 significantly attenuated sepsis‑induced lung injury and increases in IL‑1β and TNF‑α concentrations in the lung tissue. In addition, SB203580 promoted restoration of the injured lung tissue and respiratory function in CLP‑induced septic ALI model rats. The western blotting results indicated that SB203580 significantly decreased the ratios of phosphorylated (p)‑p38/p38 and p‑p65/065, and increased the protein expression levels of E‑cadherin and occludin compared with those in the ALI group. In summary, the present study demonstrated that taurine alleviated sepsis‑induced lung injury, which was associated with suppression of the inflammatory response and oxidative stress via inhibiting the p38/MAPK signaling pathway. Therefore, the p38/MAPK signaling pathway may serve as a potential therapeutic target for the treatment of sepsis‑induced ALI.

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1	Kumar V: Pulmonary Innate Immune Response Determines the Outcome of Inflammation During Pneumonia and Sepsis-Associated Acute Lung Injury. Front Immunol. 11:17222020. View Article : Google Scholar : PubMed/NCBI
2	Lelubre C and Vincent JL: Mechanisms and treatment of organ failure in sepsis. Nat Rev Nephrol. 14:417–427. 2018. View Article : Google Scholar : PubMed/NCBI
3	Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, et al: The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 315:801–810. 2016. View Article : Google Scholar : PubMed/NCBI
4	Fang WF, Huang CH, Chen YM, Hung KY, Chang YC, Lin CY, Fang YT, Chang YT, Chen HC, Huang KT, et al: Application of dynamic pulse pressure and vasopressor tools for predicting outcomes in patients with sepsis in intensive care units. J Crit Care. 52:156–162. 2019. View Article : Google Scholar : PubMed/NCBI
5	Sterling SA, Puskarich MA, Glass AF, Guirgis F and Jones AE: The Impact of the Sepsis-3 Septic Shock Definition on Previously Defined Septic Shock Patients. Crit Care Med. 45:1436–1442. 2017. View Article : Google Scholar : PubMed/NCBI
6	Li T and Zou C: The Role of Deubiquitinating Enzymes in Acute Lung Injury and Acute Respiratory Distress Syndrome. Int J Mol Sci. 21:48422020. View Article : Google Scholar : PubMed/NCBI
7	Fleischmann C, Scherag A, Adhikari NK, Hartog CS, Tsaganos T, Schlattmann P, Angus DC and Reinhart K; International Forum of Acute Care Trialists; Current Estimates and Limitations, : Assessment of Global Incidence and Mortality of Hospital-treated Sepsis. Am J Respir Crit Care Med. 193:259–272. 2016. View Article : Google Scholar : PubMed/NCBI
8	Yang L, Liu S, Han S, Hu Y, Wu Z, Shi X, Pang B, Ma Y and Jin J: The HDL from septic-ARDS patients with composition changes exacerbates pulmonary endothelial dysfunction and acute lung injury induced by cecal ligation and puncture (CLP) in mice. Respir Res. 21:2932020. View Article : Google Scholar : PubMed/NCBI
9	Qiu X, Liang X, Li H and Sun R: LPS-induced vein endothelial cell injury and acute lung injury have Btk and Orai 1 to regulate SOC-mediated calcium influx. Int Immunopharmacol. 90:1070392021. View Article : Google Scholar : PubMed/NCBI
10	Li L, Dong L, Zhao D, Gao F and Yan J: Classical dendritic cells regulate acute lung inflammation and injury in mice with lipopolysaccharide induced acute respiratory distress syndrome. Int J Mol Med. 44:617–629. 2019.PubMed/NCBI
11	Wang F, Wang M, Wang J, Chen M, Sun S, Yao S and Xia H: Maresin1 ameliorates sepsis-associated lung injury by inhibiting the activation of the JAK2/STAT3 and MAPK/ NF-κB signaling pathways. Microb Pathog. 148:1044682020. View Article : Google Scholar : PubMed/NCBI
12	Hu XH, Situ HL, Chen JP and Yu RH: Lipoxin A4 alleviates lung injury in sepsis rats through p38/MAPK signaling pathway. J Biol Reg Homeost Agents. 34:807–814. 2020.PubMed/NCBI
13	Zhang HF, Zhang HB, Wu XP, Guo YL, Cheng WD and Qian F: Fisetin alleviates sepsis-induced multiple organ dysfunction in mice via inhibiting p38 MAPK/MK2 signaling. Acta Pharmacol Sin. 41:1348–1356. 2020. View Article : Google Scholar : PubMed/NCBI
14	Shao Y, Chen X, Liu Y, Chen X, Li C, Wang L and Zhao W: Dexmedetomidine alleviates lung injury in sepsis mice through regulating P38 MAPK signaling pathway. Panminerva Med. Mar 30–2020.(Epub ahead of print). doi: 10.23736/S0031-0808.20.03885-9.
15	Feng Y, Fang Z, Liu B and Zheng X: p38MAPK plays a pivotal role in the development of acute respiratory distress syndrome. Clinics (São Paulo). 74:e5092019. View Article : Google Scholar
16	Chen X, Hu J, Pan Y and Tang Z: Novel noncoding RNAs biomarkers in acute respiratory distress syndrome. Expert Rev Respir Med. 14:299–306. 2020. View Article : Google Scholar : PubMed/NCBI
17	Jakaria M, Azam S, Haque ME, Jo SH, Uddin MS, Kim IS and Choi DK: Taurine and its analogs in neurological disorders: Focus on therapeutic potential and molecular mechanisms. Redox Biol. 24:1012232019. View Article : Google Scholar : PubMed/NCBI
18	Schaffer S and Kim HW: Effects and Mechanisms of Taurine as a Therapeutic Agent. Biomol Ther (Seoul). 26:225–241. 2018. View Article : Google Scholar : PubMed/NCBI
19	Thirupathi A, Pinho RA, Baker JS, István B and Gu Y: Taurine Reverses Oxidative Damages and Restores the Muscle Function in Overuse of Exercised Muscle. Front Physiol. 11:5824492020. View Article : Google Scholar : PubMed/NCBI
20	Zhao W, Jia L, Yang HJ, Xue X, Xu WX, Cai JQ, Guo RJ and Cao CC: Taurine enhances the protective effect of Dexmedetomidine on sepsis-induced acute lung injury via balancing the immunological system. Biomed Pharmacother. 103:1362–1368. 2018. View Article : Google Scholar : PubMed/NCBI
21	Li S, Wang J, Wei BK, Dong G and Wang X: Protective Effect of Taurine on Paraquat-Induced Lung Epithelial Cell Injury. Adv Exp Med Biol. 1155:739–746. 2019. View Article : Google Scholar : PubMed/NCBI
22	Gao Y, Li X, Gao J, Zhang Z, Feng Y, Nie J, Zhu W, Zhang S and Cao J: Metabolomic Analysis of Radiation-Induced Lung Injury in Rats: The Potential Radioprotective Role of Taurine. Dose Response. 17:1559325819883479. 2019. View Article : Google Scholar
23	Sun Z, Yang Z, Wang M, Huang C, Ren Y, Zhang W, Gao F, Cao L, Li L and Nie S: Paraquat induces pulmonary fibrosis through Wnt/β-catenin signaling pathway and myofibroblast differentiation. Toxicol Lett. 333:170–183. 2020. View Article : Google Scholar : PubMed/NCBI
24	Chen Z, Ding X, Jin S, Pitt B, Zhang L, Billiar T and Li Q: WISP1-αvβ3 integrin signaling positively regulates TLR-triggered inflammation response in sepsis induced lung injury. Sci Rep. 6:288412016. View Article : Google Scholar : PubMed/NCBI
25	Liu Q, Hua F, Deng C, Zhang J, Xu G and Hu Y: Protective and therapeutic effects of Danhong injection on acute pancreatitis associated lung injury. Mol Med Rep. 16:7603–7608. 2017. View Article : Google Scholar : PubMed/NCBI
26	Men X, Han S, Gao J, Cao G, Zhang L, Yu H, Lu H and Pu J: Taurine protects against lung damage following limb ischemia reperfusion in the rat by attenuating endoplasmic reticulum stress-induced apoptosis. Acta Orthop. 81:263–267. 2010. View Article : Google Scholar : PubMed/NCBI
27	Tanino Y, Makita H, Miyamoto K, Betsuyaku T, Ohtsuka Y, Nishihira J and Nishimura M: Role of macrophage migration inhibitory factor in bleomycin-induced lung injury and fibrosis in mice. Am J Physiol Lung Cell Mol Physiol. 283:L156–L162. 2002. View Article : Google Scholar : PubMed/NCBI
28	Sun Z, Gong X, Zhu H, Wang C, Xu X, Cui D, Qian W and Han X: Inhibition of Wnt/β-catenin signaling promotes engraftment of mesenchymal stem cells to repair lung injury. J Cell Physiol. 229:213–224. 2014. View Article : Google Scholar : PubMed/NCBI
29	Park I, Kim M, Choe K, Song E, Seo H, Hwang Y, Ahn J, Lee SH, Lee JH, Jo YH, et al: Neutrophils disturb pulmonary microcirculation in sepsis-induced acute lung injury. Eur Respir J. 53:532019. View Article : Google Scholar : PubMed/NCBI
30	Cong Z, Li D, Tao Y, Lv X and Zhu X: α2A -AR antagonism by BRL-44408 maleate attenuates acute lung injury in rats with downregulation of ERK1/2, p38MAPK, and p65 pathway. J Cell Physiol. 235:6905–6914. 2020. View Article : Google Scholar : PubMed/NCBI
31	Rhodes A, Phillips G, Beale R, Cecconi M, Chiche JD, De Backer D, Divatia J, Du B, Evans L, Ferrer R, et al: The Surviving Sepsis Campaign bundles and outcome: results from the International Multicentre Prevalence Study on Sepsis (the IMPreSS study). Intens Care Med. 41:1620–1628. 2015. View Article : Google Scholar : PubMed/NCBI
32	Machado FR, Cavalcanti AB, Bozza FA, Ferreira EM, Angotti Carrara FS, Sousa JL, Caixeta N, Salomao R, Angus DC, Pontes Azevedo LC, et al SPREAD Investigators; Latin American Sepsis Institute Network, : The epidemiology of sepsis in Brazilian intensive care units (the Sepsis PREvalence Assessment Database, SPREAD): An observational study. Lancet Infect Dis. 17:1180–1189. 2017. View Article : Google Scholar : PubMed/NCBI
33	Fan EKY and Fan J: Regulation of alveolar macrophage death in acute lung inflammation. Respir Res. 19:502018. View Article : Google Scholar : PubMed/NCBI
34	Magnani ND, Dada LA and Sznajder JI: Ubiquitin-proteasome signaling in lung injury. Transl Res. 198:29–39. 2018. View Article : Google Scholar : PubMed/NCBI
35	Matthay MA, Arabi YM, Siegel ER, Ware LB, Bos LDJ, Sinha P, Beitler JR, Wick KD, Curley MAQ, Constantin JM, et al: phenotypes and personalized medicine in the acute respiratory distress syndrome. Intensive Care Med. 46:2136–2152. 2020. View Article : Google Scholar : PubMed/NCBI
36	Masterson C, Jerkic M, Curley GF and Laffey JG: Mesenchymal stromal cell therapies: Potential and pitfalls for ARDS. Minerva Anestesiol. 81:179–194. 2015.PubMed/NCBI
37	Wang YM, Qi X, Gong FC, Chen Y, Yang ZT, Mao EQ and Chen EZ: Protective and predictive role of Mucin1 in sepsis-induced ALI/ARDS. Int Immunopharmacol. 83:1064382020. View Article : Google Scholar : PubMed/NCBI
38	Lu YF, Zhang QY, Wang LH, Liu XY and Zhang SX: The protective effects of taurine on experimental autoimmune myocarditis. Eur Rev Med Pharm. 21:1868–1875. 2017.PubMed/NCBI
39	Shao Z, Li Q, Wang S and Chen Z: Protective effects of PNU 282987 on sepsis induced acute lung injury in mice. Mol Med Rep. 19:3791–3798. 2019.PubMed/NCBI
40	Bhavsar TM, Cantor JO, Patel SN and Lau-Cam CA: Attenuating effect of taurine on lipopolysaccharide-induced acute lung injury in hamsters. Pharmacol Res. 60:418–428. 2009. View Article : Google Scholar : PubMed/NCBI
41	Cui S, Nian Q, Chen G, Wang X, Zhang J, Qiu J and Zhang Z: Ghrelin ameliorates A549 cell apoptosis caused by paraquat via p38-MAPK regulated mitochondrial apoptotic pathway. Toxicology. 426:1522672019. View Article : Google Scholar : PubMed/NCBI
42	Zhang CY, Lin SQ, Liu FY, Ma JH, Jia FJ, Han Z, Xie WD and Li X: The anti-inflammatory effect of -kaur-15-en-17-al-18-oic acid on lipopolysaccharide-stimulated RAW264.7 cells associated with NF-κB and P38/MAPK pathways. J Asian Nat Prod Res. 23:570–583. 2021. View Article : Google Scholar : PubMed/NCBI
43	Fang H, Zhang J, Ao M, He F, Chen W, Qian Y, Zhang Y, Xu Y and Fang M: Synthesis and discovery of ω-3 polyunsaturated fatty acid- alkanolamine (PUFA-AA) derivatives as anti-inflammatory agents targeting Nur77. Bioorg Chem. 105:1044562020. View Article : Google Scholar : PubMed/NCBI
44	Xiao Q, Cui Y, Zhao Y, Liu L, Wang H and Yang L: Orientin relieves lipopolysaccharide-induced acute lung injury in mice: The involvement of its anti-inflammatory and anti-oxidant properties. Int Immunopharmacol. 90:1071892021. View Article : Google Scholar : PubMed/NCBI