SB203580 protects against inflammatory response and lung injury in a mouse model of lipopolysaccharide‑induced acute lung injury

Li,Guirong; Dai,Youai; Tan,Jianxin; Zou,Jian; Nie,Xiaowei; Yang,Zhenkun; Zhao,Jingjing; Yang,Xusheng; Chen,Jingyu

doi:10.3892/mmr.2020.11214

SB203580 protects against inflammatory response and lung injury in a mouse model of lipopolysaccharide‑induced acute lung injury

Authors:
- Guirong Li
- Youai Dai
- Jianxin Tan
- Jian Zou
- Xiaowei Nie
- Zhenkun Yang
- Jingjing Zhao
- Xusheng Yang
- Jingyu Chen
View Affiliations

Affiliations: Center of Clinical Research, Wuxi People's Hospital of Nanjing Medical University, Wuxi, Jiangsu 214023, P.R. China
Published online on: June 4, 2020 https://doi.org/10.3892/mmr.2020.11214
Pages: 1656-1662

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Acute lung injury (ALI) is characterized by acute hypoxic respiratory failure, pulmonary edema and inflammatory infiltration. ALI has a high mortality rate (~30%) in the clinical setting; therefore, focusing on the treatment of lung edema and inflammatory responses in ALI is of significance. The present study investigated the effect of the p38 mitogen‑activated protein kinase (p38MAPK) inhibitor, SB203580, on lung edema and inflammatory responses in ALI in vivo. A mouse model of ALI was established to assess the effect of SB203580 on edema, proinflammatory cytokine production, and the expression of interferon regulatory factor 5 (IRF5) and inducible nitric oxide synthase (iNOS) in lung tissues using immunoblotting, immunohistochemistry, immunofluorescence, hematoxylin and eosin staining, and ELISA. SB203580 inhibited LPS‑induced lung injury and proinflammatory cytokine expression, including tumor necrosis factor‑α and interleukin‑1β. SB203580 also downregulated LPS‑induced IRF5 and iNOS expression, which are widely used as markers of proinflammatory macrophages. Collectively, the present study demonstrated that SB203580 protected against inflammatory responses and lung injury by inhibiting lung edema and downregulating proinflammatory mediators in LPS‑induced lung injury.

View Figures

View References

1	Ashbaugh DG, Bigelow DB, Petty TL and Levine BE: Acute respiratory distress in adults. Lancet. 2:319–323. 1967. View Article : Google Scholar : PubMed/NCBI
2	Villar J, Blanco J and Kacmarek RM: Current incidence and outcome of the acute respiratory distress syndrome. Curr Opin Crit Care. 22:1–6. 2016. View Article : Google Scholar : PubMed/NCBI
3	Erickson SE, Martin GS, Davis JL, Matthay MA and Eisner MD; NIH NHLBI ARDS Network, : Recent trends in acute lung injury mortality: 1996–2005. Crit Care Med. 37:1574–1579. 2009. View Article : Google Scholar : PubMed/NCBI
4	Patel BV, Wilson MR and Takata M: Resolution of acute lung injury and inflammation: A translational mouse model. Eur Respir J. 39:1162–1170. 2012. View Article : Google Scholar : PubMed/NCBI
5	Gill SE, Yamashita CM and Veldhuizen RA: Lung remodeling associated with recovery from acute lung injury. Cell Tissue Res. 367:495–509. 2017. View Article : Google Scholar : PubMed/NCBI
6	Matute-Bello G, Frevert CW and Martin TR: Animal models of acute lung injury. Am J Physiol Lung Cell Mol Physiol. 295:L379–L399. 2008. View Article : Google Scholar : PubMed/NCBI
7	Han S and Mallampalli RK: The acute respiratory distress syndrome: From mechanism to translation. J Immunol. 194:855–860. 2015. View Article : Google Scholar : PubMed/NCBI
8	Robb CT, Regan KH, Dorward DA and Rossi AG: Key mechanisms governing resolution of lung inflammation. Semin Immunopathol. 38:425–448. 2016. View Article : Google Scholar : PubMed/NCBI
9	Freire MO and Van Dyke TE: Natural resolution of inflammation. Periodontol 2000. 63:149–164. 2013. View Article : Google Scholar : PubMed/NCBI
10	Krausgruber T, Blazek K, Smallie T, Alzabin S, Lockstone H, Sahgal N, Hussell T, Feldmann M and Udalova IA: IRF5 promotes inflammatory macrophage polarization and TH1-TH17 responses. Nat Immunol. 12:231–238. 2011. View Article : Google Scholar : PubMed/NCBI
11	Lien C, Fang CM, Huso D, Livak F, Lu R and Pitha PM: Critical role of IRF-5 in regulation of B-cell differentiation. Proc Natl Acad Sci USA. 107:4664–4668. 2010. View Article : Google Scholar : PubMed/NCBI
12	Krausgruber T, Saliba D, Ryzhakov G, Lanfrancotti A, Blazek K and Udalova IA: IRF5 is required for late-phase TNF secretion by human dendritic cells. Blood. 115:4421–4430. 2010. View Article : Google Scholar : PubMed/NCBI
13	Aggarwal NR, King LS and D'Alessio FR: Diverse macrophage populations mediate acute lung inflammation and resolution. Am J Physiol Lung Cell Mol Physiol. 306:L709–L725. 2014. View Article : Google Scholar : PubMed/NCBI
14	Schnyder-Candrian S, Quesniaux VF, Di Padova F, Maillet I, Noulin N, Couillin I, Moser R, Erard F, Vargaftig BB, Ryffel B, et al: Dual effects of p38 MAPK on TNF-dependent bronchoconstriction and TNF-independent neutrophil recruitment in lipopolysaccharide-induced acute respiratory distress syndrome. J Immunol. 175:262–269. 2005. View Article : Google Scholar : PubMed/NCBI
15	Szarka RJ, Wang N, Gordon L, Nation PN and Smith RH: A murine model of pulmonary damage induced by lipopolysaccharide via intranasal instillation. J Immunol Methods. 202:49–57. 1997. View Article : Google Scholar : PubMed/NCBI
16	Chen H, Bai C and Wang X: The value of the lipopolysaccharide-induced acute lung injury model in respiratory medicine. Expert Rev Respir Med. 4:773–783. 2010. View Article : Google Scholar : PubMed/NCBI
17	van Helden HP, Kuijpers WC, Steenvoorden D, Go C, Bruijnzeel PL, van Eijk M and Haagsman HP: Intratracheal aerosolization of endotoxin (LPS) in the rat: A comprehensive animal model to study adult (acute) respiratory distress syndrome. Exp Lung Res. 23:297–316. 1997. View Article : Google Scholar : PubMed/NCBI
18	Matute-Bello G, Downey G, Moore BB, Groshong SD, Matthay MA, Slutsky AS and Kuebler WM; Acute Lung Injury in Animals Study Group, : An official American Thoracic Society workshop report: Features and measurements of experimental acute lung injury in animals. Am J Respir Cell Mol Biol. 44:725–738. 2011. View Article : Google Scholar : PubMed/NCBI
19	Mehta S: The effects of nitric oxide in acute lung injury. Vascul Pharmacol. 43:390–403. 2005. View Article : Google Scholar : PubMed/NCBI
20	Taylor PR, Martinez-Pomares L, Stacey M, Lin HH, Brown GD and Gordon S: Macrophage receptors and immune recognition. Annu Rev Immunol. 23:901–944. 2005. View Article : Google Scholar : PubMed/NCBI
21	Gordon S and Mantovani A: Diversity and plasticity of mononuclear phagocytes. Eur J Immunol. 41:2470–2472. 2011. View Article : Google Scholar : PubMed/NCBI
22	Hughes KT and Beasley MB: Pulmonary manifestations of acute lung injury: More than just diffuse alveolar damage. Arch Pathol Lab Med. 141:916–922. 2017. View Article : Google Scholar : PubMed/NCBI
23	Butt Y, Kurdowska A and Allen TC: Acute Lung Injury: A Clinical and Molecular Review. Arch Pathol Lab Med. 140:345–350. 2016. View Article : Google Scholar : PubMed/NCBI
24	Elicker BM, Jones KT, Naeger DM and Frank JA: Imaging of Acute Lung Injury. Radiol Clin North Am. 54:1119–1132. 2016. View Article : Google Scholar : PubMed/NCBI
25	Pyee Y, Chung HJ, Choi TJ, Park HJ, Hong JY, Kim JS, Kang SS and Lee SK: Suppression of inflammatory responses by handelin, a guaianolide dimer from Chrysanthemum boreale, via downregulation of NF-κB signaling and pro-inflammatory cytokine production. J Nat Prod. 77:917–924. 2014. View Article : Google Scholar : PubMed/NCBI
26	Nick JA, Young SK, Brown KK, Avdi NJ, Arndt PG, Suratt BT, Janes MS, Henson PM and Worthen GS: Role of p38 mitogen-activated protein kinase in a murine model of pulmonary inflammation. J Immunol. 164:2151–2159. 2000. View Article : Google Scholar : PubMed/NCBI
27	Li C, Yang D, Cao X, Wang F, Jiang H, Guo H, Du L, Guo Q and Yin X: LFG-500, a newly synthesized flavonoid, attenuates lipopolysaccharide-induced acute lung injury and inflammation in mice. Biochem Pharmacol. 113:57–69. 2016. View Article : Google Scholar : PubMed/NCBI
28	Eames HL, Corbin AL and Udalova IA: Interferon regulatory factor 5 in human autoimmunity and murine models of autoimmune disease. Transl Res. 167:167–182. 2016. View Article : Google Scholar : PubMed/NCBI
29	Khoyratty TE and Udalova IA: Diverse mechanisms of IRF5 action in inflammatory responses. Int J Biochem Cell Biol. 99:38–42. 2018. View Article : Google Scholar : PubMed/NCBI
30	Weiss M, Blazek K, Byrne AJ, Perocheau DP and Udalova IA: IRF5 is a specific marker of inflammatory macrophages in vivo. Mediators Inflamm. 2013:2458042013. View Article : Google Scholar : PubMed/NCBI
31	Cook HT, Jansen A, Lewis S, Largen P, O'Donnell M, Reaveley D and Cattell V: Arginine metabolism in experimental glomerulonephritis: Interaction between nitric oxide synthase and arginase. Am J Physiol. 267:F646–F653. 1994.PubMed/NCBI
32	Li Z, Zhao ZJ, Zhu XQ, Ren QS, Nie FF, Gao JM, Gao XJ, Yang TB, Zhou WL, Shen JL, et al: Differences in iNOS and arginase expression and activity in the macrophages of rats are responsible for the resistance against T. gondii infection. PLoS One. 7:e358342012. View Article : Google Scholar : PubMed/NCBI PubMed/NCBI PubMed/NCBI