Modulation of mitogen‑activated protein kinase attenuates sepsis‑induced acute lung injury in acute respiratory distress syndrome rats

Fang,Wei; Cai,Shi‑Xia; Wang,Chuan‑Lei; Sun,Xiao‑Xia; Li,Kun; Yan,Xiao‑Wen; Sun,Yun‑Bo; Sun,Xiao‑Zhe; Gu,Chuan‑Kai; Dai,Ming‑Ying; Wang,Hui‑Ming; Zhou,Zhen

doi:10.3892/mmr.2017.7811

Modulation of mitogen‑activated protein kinase attenuates sepsis‑induced acute lung injury in acute respiratory distress syndrome rats

Authors:
- Wei Fang
- Shi‑Xia Cai
- Chuan‑Lei Wang
- Xiao‑Xia Sun
- Kun Li
- Xiao‑Wen Yan
- Yun‑Bo Sun
- Xiao‑Zhe Sun
- Chuan‑Kai Gu
- Ming‑Ying Dai
- Hui‑Ming Wang
- Zhen Zhou
View Affiliations

Affiliations: Department of Critical Care Medicine, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China
Published online on: October 17, 2017 https://doi.org/10.3892/mmr.2017.7811
Pages: 9652-9658

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

Sepsis is the most important predisposing cause inducing acute respiratory distress syndrome (ARDS); however, the mechanism of sepsis leading to the development of ARDS remains to be elucidated. Suppression of the mitogen‑activated protein kinase (MAPK) signal by blocking the phosphorylation of Jun N‑terminal kinase (JNK) and p38 in lung tissues could alleviate acute lung injury induced by sepsis. MAPK signaling may have a crucial role in development of the sepsis‑induced acute lung injury. The specific inhibitors of JNK and p38 MAPK, SP600125 and SB203580, were administrated by intragastric injection 4 h before induction of ARDS after cecal ligation and puncture (CLP). Rats were sacrificed at 1, 6 or 24 h after CLP challenge. The histological evaluation, lung water content, and biochemical analysis were performed. The results revealed that the JNK and p38 MAPK inhibitor improved lung permeability, attenuated system inflammation, further alleviated the lung injury induced by sepsis. In conclusion, JNK and p38 MAPK signaling are essential for the development of ARDS following sepsis. Further studies are needed to illuminate the detailed mechanisms of JNK and p38 MAPK signaling in sepsis‑induced ARDS.

View Figures

View References

1	Ware LB and Matthay MA: The acute respiratory distress syndrome. N Engl J Med. 342:1334–1349. 2000. View Article : Google Scholar : PubMed/NCBI
2	Rubenfeld GD, Caldwell E, Peabody E, Weaver J, Martin DP, Neff M, Stern EJ and Hudson LD: Incidence and outcomes of acute lung injury. N Engl J Med. 353:1685–1693. 2005. View Article : Google Scholar : PubMed/NCBI
3	Goss CH, Brower RG, Hudson LD and Rubenfeld GD; ARDS Network, : Incidence of acute lung injury in the United States. Crit Care Med. 31:1607–1611. 2003. View Article : Google Scholar : PubMed/NCBI
4	Hudson LD, Milberg JA, Anardi D and Maunder RJ: Clinical risks for development of the acute respiratory distress syndrome. Am J Respir Crit Care Med. 151:293–301. 1995. View Article : Google Scholar : PubMed/NCBI
5	Sevransky JE, Martin GS, Shanholtz C, Mendez-Tellez PA, Pronovost P, Brower R and Needham DM: Mortality in sepsis versus non-sepsis induced acute lung injury. Crit Care. 13:R1502009. View Article : Google Scholar : PubMed/NCBI
6	de Luis Cabezon N, Sánchez Castro I, Uriarte UX Bengoetxea, Casanova MP Rodrigo, García Peña JM and Celorrio L Aguilera: Acute respiratory distress syndrome: A review of the Berlin definition. Rev Esp Anestesiol Reanim. 61:319–327. 2014.(In Spanish). PubMed/NCBI
7	Kono H and Rock KL: How dying cells alert the immune system to danger. Nat Rev Immunol. 8:279–289. 2008. View Article : Google Scholar : PubMed/NCBI
8	Iyer SS, Pulskens WP, Sadler JJ, Butter LM, Teske GJ, Ulland TK, Eisenbarth SC, Florquin S, Flavell RA, Leemans JC and Sutterwala FS: Necrotic cells trigger a sterile inflammatory response through the Nlrp3 inflammasome. Proc Natl Acad Sci USA. 106:pp. 20388–932. 2009; View Article : Google Scholar : PubMed/NCBI
9	Strassheim D, Park JS and Abraham E: Sepsis: Current concepts in intracellular signaling. Int J Biochem Cell Biol. 34:1527–1533. 2002. View Article : Google Scholar : PubMed/NCBI
10	Arthur JS and Ley LC: Mitogen-activated protein kinases in innate immunity. Nat Rev Immunol. 13:679–692. 2013. View Article : Google Scholar : PubMed/NCBI
11	Kyriakis JM and Avruch J: Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiol Rev. 81:807–869. 2001.PubMed/NCBI
12	Ahmed AU, Williams BR and Hannigan GE: Transcriptional Activation of Inflammatory Genes: Mechanistic insight into selectivity and diversity. Biomolecules. 5:3087–3111. 2015. View Article : Google Scholar : PubMed/NCBI
13	Cohen P: Targeting protein kinases for the development of anti-inflammatory drugs. Curr Opin Cell Biol. 21:317–324. 2009. View Article : Google Scholar : PubMed/NCBI
14	Dar AC and Shokat KM: The evolution of protein kinase inhibitors from antagonists to agonists of cellular signaling. Annu Rev Biochem. 80:769–795. 2011. View Article : Google Scholar : PubMed/NCBI
15	Kim SJ, Baek KS, Park HJ, Jung YH and Lee SM: Compound 9a, a novel synthetic histone deacetylase inhibitor, protects against septic injury in mice by suppressing MAPK signalling. Br J Pharmacol. 173:1045–1057. 2016. View Article : Google Scholar : PubMed/NCBI
16	Huang X, Kong G, Li Y, Zhu W, Xu H, Zhang X, Li J, Wang L, Zhang Z, Wu Y, et al: Decitabine and 5-azacitidine both alleviate LPS induced ARDS through anti-inflammatory/antioxidant activity and protection of glycocalyx and inhibition of MAPK pathways in mice. Biomed Pharmacother. 84:447–453. 2016. View Article : Google Scholar : PubMed/NCBI
17	Peng S, Hang N, Liu W, Guo W, Jiang C, Yang X, Xu Q and Sun Y: Andrographolide sulfonate ameliorates lipopolysaccharide-induced acute lung injury in mice by down-regulating MAPK and NF-κB pathways. Acta Pharm Sin B. 6:205–211. 2016. View Article : Google Scholar : PubMed/NCBI
18	Xu X, Liu N, Zhang YX, Cao J, Wu D, Peng Q, Wang HB and Sun WC: The protective effects of HJB-1, a derivative of 17-Hydroxy-Jolkinolide B, on LPS-induced acute distress respiratory syndrome mice. Molecules. 21:772016. View Article : Google Scholar : PubMed/NCBI
19	Kong G, Huang X, Wang L, Li Y, Sun T, Han S, Zhu W, Ma M, Xu H, Li J, et al: Astilbin alleviates LPS-induced ARDS by suppressing MAPK signaling pathway and protecting pulmonary endothelial glycocalyx. Int Immunopharmacol. 36:51–58. 2016. View Article : Google Scholar : PubMed/NCBI
20	Zhao H, Zhao M, Wang Y, Li F and Zhang Z: Glycyrrhizic acid prevents sepsis-induced acute lung injury and mortality in rats. J Histochem Cytochem. 64:125–137. 2016. View Article : Google Scholar : PubMed/NCBI
21	Shen L, Mo H, Cai L, Kong T, Zheng W, Ye J, Qi J and Xiao Z: Losartan prevents sepsis-induced acute lung injury and decreases activation of nuclear factor kappaB and mitogen-activated protein kinases. Shock. 31:500–506. 2009. View Article : Google Scholar : PubMed/NCBI
22	Otero-Antón E, González-Quintela A, López-Soto A, López-Ben S, Llovo J and Pérez LF: Cecal ligation and puncture as a model of sepsis in the rat: Influence of the puncture size on mortality, bacteremia, endotoxemia and tumor necrosis factor alpha levels. Eur Surg Res. 33:77–79. 2001. View Article : Google Scholar : PubMed/NCBI
23	Mrozek JD, Smith KM, Bing DR, Meyers PA, Simonton SC, Connett JE and Mammel MC: Exogenous surfactant and partial liquid ventilation: Physiologic and pathologic effects. Am J Respir Crit Care Med. 156:1058–1065. 1997. View Article : Google Scholar : PubMed/NCBI
24	Dolinay T, Kim YS, Howrylak J, Hunninghake GM, An CH, Fredenburgh L, Massaro AF, Rogers A, Gazourian L, Nakahira K, et al: Inflammasome-regulated cytokines are critical mediators of acute lung injury. Am J Respir Crit Care Med. 185:1225–1234. 2012. View Article : Google Scholar : PubMed/NCBI
25	Matthay MA, Zimmerman GA, Esmon C, Bhattacharya J, Coller B, Doerschuk CM, Floros J, Gimbrone MA Jr, Hoffman E, Hubmayr RD, et al: Future research directions in acute lung injury: summary of a National Heart, Lung and Blood Institute working group. Am J Respir Crit Care Med. 167:1027–1035. 2003. View Article : Google Scholar : PubMed/NCBI
26	Wu H, Zhao G, Jiang K, Chen X, Zhu Z, Qiu C, Li C and Deng G: Plantamajoside ameliorates lipopolysaccharide-induced acute lung injury via suppressing NF-κB and MAPK activation. Int Immunopharmacol. 35:315–322. 2016. View Article : Google Scholar : PubMed/NCBI
27	Lee JH, Ko HJ, Woo ER, Lee SK, Moon BS, Lee CW, Mandava S, Samala M, Lee J and Kim HP: Moracin M inhibits airway inflammation by interrupting the JNK/c-Jun and NF-κB pathways in vitro and in vivo. Eur J Pharmacol. 783:64–72. 2016. View Article : Google Scholar : PubMed/NCBI
28	Newton K and Dixit VM: Signaling in innate immunity and inflammation. Cold Spring Harb Perspect Biol. 4:pii: a0060492012. View Article : Google Scholar
29	Kawai T and Akira S: The role of pattern-recognition receptors in innate immunity: Update on Toll-like receptors. Nat Immunol. 11:373–384. 2010. View Article : Google Scholar : PubMed/NCBI
30	Medzhitov R and Horng T: Transcriptional control of the inflammatory response. Nat Rev Immunol. 9:692–703. 2009. View Article : Google Scholar : PubMed/NCBI
31	Pizzino G, Bitto A, Pallio G, Irrera N, Galfo F, Interdonato M, Mecchio A, De Luca F, Minutoli L, Squadrito F and Altavilla D: Blockade of the JNK signalling as a rational therapeutic approach to modulate the early and late steps of the inflammatory cascade in polymicrobial sepsis. Mediators Inflamm. 2015:5915722015. View Article : Google Scholar : PubMed/NCBI
32	Zhou H, Bian D, Jiao X, Wei Z, Zhang H, Xia Y, He Y and Dai Y: Paeoniflorin protects against lipopolysaccharide-induced acute lung injury in mice by alleviating inflammatory cell infiltration and microvascular permeability. Inflamm Res. 60:981–990. 2011. View Article : Google Scholar : PubMed/NCBI
33	Zhu X, Zou Y, Wang B, Zhu J, Chen Y, Wang L, Li J and Deng X: Blockade of CXC chemokine receptor 3 on endothelial cells protects against sepsis-induced acute lung injury. J Surg Res. 204:288–296. 2016. View Article : Google Scholar : PubMed/NCBI
34	Rahman A and Fazal F: Blocking NF-κB: An inflammatory issue. Proc Am Thorac Soc. 8:pp. 497–503. 2011; View Article : Google Scholar : PubMed/NCBI
35	McKenna S and Wright CJ: Inhibiting IκBβ-NFκB signaling attenuates the expression of select pro-inflammatory genes. J Cell Sci. 128:2143–2155. 2015. View Article : Google Scholar : PubMed/NCBI
36	Lee IT and Yang CM: Inflammatory signalings involved in airway and pulmonary diseases. Mediators Inflamm. 2013:7912312013. View Article : Google Scholar : PubMed/NCBI
37	Lai JL, Liu YH, Liu C, Qi MP, Liu RN, Zhu XF, Zhou QG, Chen YY, Guo AZ and Hu CM: Indirubin Inhibits LPS-induced inflammation via TLR4 abrogation mediated by the NF-kB and MAPK signaling pathways. Inflammation. 40:1–12. 2017. View Article : Google Scholar : PubMed/NCBI
38	Guo X, Gerl RE and Schrader JW: Defining the involvement of p38alpha MAPK in the production of anti- and proinflammatory cytokines using an SB 203580-resistant form of the kinase. J Biol Chem. 278:22237–22242. 2003. View Article : Google Scholar : PubMed/NCBI
39	Jeong HJ, Na HJ, Hong SH and Kim HM: Inhibition of the stem cell factor-induced migration of mast cells by dexamethasone. Endocrinology. 144:4080–4086. 2003. View Article : Google Scholar : PubMed/NCBI
40	Schafer PH, Wang L, Wadsworth SA, Davis JE and Siekierka JJ: T cell activation signals up-regulate p38 mitogen-activated protein kinase activity and induce TNF-alpha production in a manner distinct from LPS activation of monocytes. J Immunol. 162:659–568. 1999.PubMed/NCBI
41	Beyaert R, Cuenda A, Berghe W Vanden, Plaisance S, Lee JC, Haegeman G, Cohen P and Fiers W: The p38/RK mitogen-activated protein kinase pathway regulates interleukin-6 synthesis response to tumor necrosis factor. EMBO J. 15:1914–1923. 1996.PubMed/NCBI
42	Foey AD, Parry SL, Williams LM, Feldmann M, Foxwell BM and Brennan FM: Regulation of monocyte IL-10 synthesis by endogenous IL-1 and TNF-alpha: Role of the p38 and p42/44 mitogen-activated protein kinases. J Immunol. 160:920–928. 1998.PubMed/NCBI
43	Koprak S, Staruch MJ and Dumont FJ: A specific inhibitor of the p38 mitogen activated protein kinase affects differentially the production of various cytokines by activated human T cells: Dependence on CD28 signaling and preferential inhibition of IL-10 production. Cell Immunol. 192:87–95. 1999. View Article : Google Scholar : PubMed/NCBI
44	Yu X, Yu S, Chen L, Liu H, Zhang J, Ge H, Zhang Y, Yu B and Kou J: Tetrahydroberberrubine attenuates lipopolysaccharide-induced acute lung injury by down-regulating MAPK, AKT, and NF-κB signaling pathways. Biomed Pharmacother. 82:489–497. 2016. View Article : Google Scholar : PubMed/NCBI
45	Jeong HW, Hsu KC, Lee JW, Ham M, Huh JY, Shin HJ, Kim WS and Kim JB: Berberine suppresses proinflammatory responses through AMPK activation in macrophages. Am J Physiol Endocrinol Metab. 296:E955–E964. 2009. View Article : Google Scholar : PubMed/NCBI
46	Yeh CC, Kao SJ, Lin CC, Wang SD, Liu CJ and Kao ST: The immunomodulation of endotoxin-induced acute lung injury by hesperidin in vivo and in vitro. Life Sci. 80:1821–1831. 2007. View Article : Google Scholar : PubMed/NCBI
47	Singleton KD, Beckey VE and Wischmeyer PE: Glutamine prevents activation of NF-kappaB and stress kinase pathways, attenuates inflammatory cytokine release, and prevents acute respiratory distress syndrome (ARDS) following sepsis. Shock. 24:583–589. 2005. View Article : Google Scholar : PubMed/NCBI
48	Yang HT, Papoutsopoulou S, Belich M, Brender C, Janzen J, Gantke T, Handley M and Ley SC: Coordinate regulation of TPL-2 and NF-κB signaling in macrophages by NF-κB1 p105. Mol Cell Biol. 32:3438–3451. 2012. View Article : Google Scholar : PubMed/NCBI