Macrophage migration inhibitory factor antagonist (S,R)3‑(4‑hydroxyphenyl)‑4,5‑dihydro‑5‑isoxazole acetic acid methyl ester attenuates inflammation and lung injury in rats with acute pancreatitis in pregnancy

Zhou,Yu; Zhao,Liang; Mei,Fangchao; Hong,Yupu; Xia,He; Zuo,Teng; Ding,Youming; Wang,Weixing

doi:10.3892/mmr.2018.8672

Macrophage migration inhibitory factor antagonist (S,R)3‑(4‑hydroxyphenyl)‑4,5‑dihydro‑5‑isoxazole acetic acid methyl ester attenuates inflammation and lung injury in rats with acute pancreatitis in pregnancy

Authors:
- Yu Zhou
- Liang Zhao
- Fangchao Mei
- Yupu Hong
- He Xia
- Teng Zuo
- Youming Ding
- Weixing Wang
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Affiliations: Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
Published online on: March 1, 2018 https://doi.org/10.3892/mmr.2018.8672
Pages: 6576-6584
Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine involved in many acute and chronic inflammatory diseases. However, its role in acute lung injury associated with acute pancreatitis in pregnancy (APIP) has not yet been elucidated. The present study was undertaken to clarify the effect and potential mechanism of MIF antagonist (S,R)3‑(4‑hydroxyphenyl)‑4,5‑dihydro‑5‑isoxazole acetic acid methyl ester (ISO‑1) in the development of acute lung injury in rats with APIP. Eighteen late‑gestation SD rats were randomly assigned to three groups: Sham operation (SO) group, APIP group, and ISO‑1 group. All the rats were sacrificed 6 h after modeling. The severity of pancreatitis was evaluated by serum amylase (AMY), lipase (LIPA), tumor necrosis factor (TNF)‑α, interleukin (IL)‑1β and IL‑6 and assessing the histopathological score. Lung injury was determined by performing histology and inflammatory cell infiltration investigations. Western blot analysis was used to detect the protein expression of MIF, phosphorylated and total P38 and nuclear factor‑κB (NF‑κB) protein in lungs. The results showed that MIF was upregulated in the lung of APIP rats. Compared with APIP group, the intervention of ISO‑1 alleviated the pathological injury of the pancreas and lungs, decreased serum AMY and LIPA, attenuated serum concentrations of TNF‑α, IL‑1β, and IL‑6, reduced the number of MPO‑positive cells in the lung and inhibited the activation of P38MAPK and NF‑κB. These results suggest that MIF is activated in lung injury induced by APIP. Furhtermore, the present findings indicate that the MIF antagonist ISO‑1 has a protective effect on lung injury and inflammation, which may be associated with deactivating the P38MAPK and NF‑κB signaling pathway.

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1	Mali P: Pancreatitis in pregnancy: Etiology, diagnosis, treatment, and outcomes. Hepatobiliary Pancreat Dis Int. 15:434–438. 2016. View Article : Google Scholar : PubMed/NCBI
2	Zuo T, Yu J, Wang WX, Zhao KL, Chen C, Deng WH, He XB, Wang P, Shi Q and Guo WY: Mitogen-activated protein kinases are activated in placental injury in rat model of acute pancreatitis in pregnancy. Pancreas. 45:850–857. 2016. View Article : Google Scholar : PubMed/NCBI
3	Akcakaya A, Ozkan OV, Okan I, Kocaman O and Sahin M: Endoscopic retrograde cholangiopancreatography during pregnancy without radiation. World J Gastroenterol. 15:3649–3652. 2009. View Article : Google Scholar : PubMed/NCBI
4	Hernandez A, Petrov MS, Brooks DC, Banks PA, Ashley SW and Tavakkolizadeh A: Acute pancreatitis and pregnancy: A 10-year single center experience. J Gastrointest Surg. 11:1623–1627. 2007. View Article : Google Scholar : PubMed/NCBI
5	Halonen KI, Pettilä V, Leppäniemi AK, Kemppainen EA, Puolakkainen PA and Haapiainen RK: Multiple organ dysfunction associated with severe acute pancreatitis. Crit Care Med. 30:1274–1279. 2002. View Article : Google Scholar : PubMed/NCBI
6	Mole DJ, Webster SP, Uings I, Zheng X, Binnie M, Wilson K, Hutchinson JP, Mirguet O, Walker A, Beaufils B, et al: Kynurenine-3-monooxygenase inhibition prevents multiple organ failure in rodent models of acute pancreatitis. Nat Med. 22:202–209. 2016. View Article : Google Scholar : PubMed/NCBI
7	Elder AS, Saccone GT and Dixon DL: Lung injury in acute pancreatitis: Mechanisms underlying augmented secondary injury. Pancreatology. 12:49–56. 2012. View Article : Google Scholar : PubMed/NCBI
8	Pastor CM, Matthay MA and Frossard JL: Pancreatitis-associated acute lung injury: New insights. Chest. 124:2341–2351. 2003. View Article : Google Scholar : PubMed/NCBI
9	Jaffray C, Yang J, Carter G, Mendez C and Norman J: Pancreatic elastase activates pulmonary nuclear factor kappa B and inhibitory kappa B, mimicking pancreatitis-associated adult respiratory distress syndrome. Surgery. 128:225–231. 2000. View Article : Google Scholar : PubMed/NCBI
10	Lu H and Bai Y, Wu L, Hong W, Liang Y, Chen B and Bai Y: Inhibition of macrophage migration inhibitory factor protects against inflammation and matrix deposition in kidney tissues after injury. Mediat Inflamm. 2016:21746822016. View Article : Google Scholar
11	Leng L, Metz CN, Fang Y, Xu J, Donnelly S, Baugh J, Delohery T, Chen Y, Mitchell RA and Bucala R: MIF signal transduction initiated by binding to CD74. J Exp Med. 197:1467–1476. 2003. View Article : Google Scholar : PubMed/NCBI
12	Lue H, Thiele M, Franz J, Dahl E, Speckgens S, Leng L, Fingerle-Rowson G, Bucala R, Lüscher B and Bernhagen J: Macrophage migration inhibitory factor (MIF) promotes cell survival by activation of the Akt pathway and role for CSN5/JAB1 in the control of autocrine MIF activity. Oncogene. 26:5046–5059. 2007. View Article : Google Scholar : PubMed/NCBI
13	Gao Y, Hou R, Liu F, Liu H, Fei Q, Han Y, Cai R, Peng C and Qi Y: Obacunone causes sustained expression of MKP-1 thus inactivating p38 MAPK to suppress pro-inflammatory mediators through intracellular MIF. J Cell Biochem. 119:837–849. 2018. View Article : Google Scholar : PubMed/NCBI
14	Roger T, Schneider A, Weier M, Sweep FC, Le Roy D, Bernhagen J, Calandra T and Giannoni E: High expression levels of macrophage migration inhibitory factor sustain the innate immune responses of neonates. Proc Natl Acad Sci USA. 113:pp. E997–E1005. 2016; View Article : Google Scholar : PubMed/NCBI
15	Aeberli D, Leech M and Morand EF: Macrophage migration inhibitory factor and glucocorticoid sensitivity. Rheumatology (Oxford). 45:937–943. 2006. View Article : Google Scholar : PubMed/NCBI
16	Calandra T, Echtenacher B, Roy DL, Pugin J, Metz CN, Hültner L, Heumann D, Männel D, Bucala R and Glauser MP: Protection from septic shock by neutralization of macrophage migration inhibitory factor. Nat Med. 6:164–170. 2000. View Article : Google Scholar : PubMed/NCBI
17	Al-Abed Y, Dabideen D, Aljabari B, Valster A, Messmer D, Ochani M, Tanovic M, Ochani K, Bacher M, Nicoletti F, et al: ISO-1 binding to the tautomerase active site of MIF inhibits its pro-inflammatory activity and increases survival in severe sepsis. J Biol Chem. 280:36541–36544. 2005. View Article : Google Scholar : PubMed/NCBI
18	Bozza FA, Gomes RN, Japiassú AM, Soares M, Castro-Faria-Neto HC, Bozza PT and Bozza MT: Macrophage migration inhibitory factor levels correlate with fatal outcome in sepsis. Shock. 22:309–313. 2004. View Article : Google Scholar : PubMed/NCBI
19	Mikulowska A, Metz CN, Bucala R and Holmdahl R: Macrophage migration inhibitory factor is involved in the pathogenesis of collagen type II-induced arthritis in mice. J Immunol. 158:5514–5517. 1997.PubMed/NCBI
20	Amano T, Nishihira J and Miki I: Blockade of macrophage migration inhibitory factor (MIF) prevents the antigen-induced response in a murine model of allergic airway inflammation. Inflamm Res. 56:24–31. 2007. View Article : Google Scholar : PubMed/NCBI
21	Ohkawara T, Nishihira J, Takeda H, Hige S, Kato M, Sugiyama T, Iwanaga T, Nakamura H, Mizue Y and Asaka M: Amelioration of dextran sulfate sodium-induced colitis by anti-macrophage migration inhibitory factor antibody in mice. Gastroenterology. 123:256–270. 2002. View Article : Google Scholar : PubMed/NCBI
22	Russell KE, Chung KF, Clarke CJ, Durham AL, Mallia P, Footitt J, Johnston SL, Barnes PJ, Hall SR, Simpson KD, et al: The MIF antagonist ISO-1 attenuates corticosteroid-insensitive inflammation and airways hyperresponsiveness in an ozone-induced model of COPD. PLoS One. 11:e1461022016. View Article : Google Scholar
23	West PW, Parker LC, Ward JR and Sabroe I: Differential and cell-type specific regulation of responses to Toll-like receptor agonists by ISO-1. Immunology. 125:101–110. 2008. View Article : Google Scholar : PubMed/NCBI
24	Yu J, Deng W, Wang W, Ding Y, Jin H, Chen C, Chen X, Xiong X and Xu S: Inhibition of poly(ADP-ribose) polymerase attenuates acute kidney injury in sodium taurocholate-induced acute pancreatitis in rats. Pancreas. 41:1299–1305. 2012. View Article : Google Scholar : PubMed/NCBI
25	Mei F, Shi Q, Zuo T, Chen C, Wang P, Li C, He B, Yang X, Hu P and Wang W: Dose-effect relationship and protective effect of MIF inhibitor on pancreas and placenta injuries in rats with acute necrotizing pancreatitis in late pregnancy. Chin J Emerg Med. 25:45–49. 2016.
26	Schmidt J, Rattner DW, Lewandrowski K, Compton CC, Mandavilli U, Knoefel WT and Warshaw AL: A better model of acute pancreatitis for evaluating therapy. Ann Surg. 215:44–56. 1992. View Article : Google Scholar : PubMed/NCBI
27	Werner J, Z'Graggen K, Fernández-del Castillo C, Lewandrowski KB, Compton CC and Warshaw AL: Specific therapy for local and systemic complications of acute pancreatitis with monoclonal antibodies against ICAM-1. Ann Surg. 229:834–842. 1999. View Article : Google Scholar : PubMed/NCBI
28	Sha H, Ma Q, Jha RK and Wang Z: Resveratrol ameliorates lung injury via inhibition of apoptosis in rats with severe acute pancreatitis. Exp Lung Res. 35:344–358. 2009. View Article : Google Scholar : PubMed/NCBI
29	Nishiki Y, Adewola A, Hatanaka M, Templin AT, Maier B and Mirmira RG: Translational control of inducible nitric oxide synthase by p38 MAPK in islet β-cells. Mol Endocrinol. 27:336–349. 2013. View Article : Google Scholar : PubMed/NCBI
30	Que RS, Cao LP, Ding GP, Hu JA, Mao KJ and Wang GF: Correlation of nitric oxide and other free radicals with the severity of acute pancreatitis and complicated systemic inflammatory response syndrome. Pancreas. 39:536–540. 2010. View Article : Google Scholar : PubMed/NCBI
31	Kim K, Li Y, Jin G, Chong W, Liu B, Lu J, Lee K, Demoya M, Velmahos GC and Alam HB: Effect of valproic acid on acute lung injury in a rodent model of intestinal ischemia reperfusion. Resuscitation. 83:243–248. 2012. View Article : Google Scholar : PubMed/NCBI
32	Bargagli E, Olivieri C, Nikiforakis N, Cintorino M, Magi B, Perari MG, Vagaggini C, Spina D, Prasse A and Rottoli P: Analysis of macrophage migration inhibitory factor (MIF) in patients with idiopathic pulmonary fibrosis. Respir Physiol Neurobiol. 167:261–267. 2009. View Article : Google Scholar : PubMed/NCBI
33	Heinrichs D, Knauel M, Offermanns C, Berres ML, Nellen A, Leng L, Schmitz P, Bucala R, Trautwein C, Weber C, et al: Macrophage migration inhibitory factor (MIF) exerts antifibrotic effects in experimental liver fibrosis via CD74. Proc Natl Acad Sci USA. 108:pp. 17444–17449. 2011; View Article : Google Scholar : PubMed/NCBI
34	Jaworek J, Jachimczak B, Tomaszewska R, Konturek PC, Pawlik WW, Sendur R, Hahn EG, Stachura J and Konturek SJ: Protective action of lipopolysaccharidesin rat caerulein-induced pancreatitis: Role of nitric oxide. Digestion. 62:1–13. 2000. View Article : Google Scholar : PubMed/NCBI
35	Gao Y, Liu F, Fang L, Cai R, Zong C and Qi Y: Genkwanin inhibits proinflammatory mediators mainly through the regulation of miR-101/MKP-1/MAPK pathway in LPS-activated macrophages. PLoS One. 9:e967412014. View Article : Google Scholar : PubMed/NCBI
36	Choi SB, Bae GS, Jo IJ, Wang S, Song HJ and Park SJ: Berberine inhibits inflammatory mediators and attenuates acute pancreatitis through deactivation of JNK signaling pathways. Mol Immunol. 74:27–38. 2016. View Article : Google Scholar : PubMed/NCBI
37	Geng Y, Li W, Sun L, Tong Z, Li N and Li J: Severe acute pancreatitis during pregnancy: Eleven years experience from a surgical intensive care unit. Dig Dis Sci. 56:3672–3677. 2011. View Article : Google Scholar : PubMed/NCBI
38	Stimac D and Stimac T: Acute pancreatitis during pregnancy. Eur J Gastroenterol Hepatol. 23:839–844. 2011. View Article : Google Scholar : PubMed/NCBI
39	Hacker FM, Whalen PS, Lee VR and Caughey AB: Maternal and fetal outcomes of pancreatitis in pregnancy. Am J Obstet Gynecol. 213:568.e1–5. 2015. View Article : Google Scholar
40	Robertson KW, Stewart IS and Imrie CW: Severe acute pancreatitis and pregnancy. Pancreatology. 6:309–315. 2006. View Article : Google Scholar : PubMed/NCBI
41	Rahman SH, Menon KV, Holmfield JH, McMahon MJ and Guillou JP: Serum macrophage migration inhibitory factor is an early marker of pancreatic necrosis in acute pancreatitis. Ann Surg. 245:282–289. 2007. View Article : Google Scholar : PubMed/NCBI
42	Barnes MA, McMullen MR, Roychowdhury S, Pisano SG, Liu X, Stavitsky AB, Bucala R and Nagy LE: Macrophage migration inhibitory factor contributes to ethanol-induced liver injury by mediating cell injury, steatohepatitis, and steatosis. Hepatology. 57:1980–1991. 2013. View Article : Google Scholar : PubMed/NCBI
43	Lai KN, Leung JC, Metz CN, Lai FM, Bucala R and Lan HY: Role for macrophage migration inhibitory factor in acute respiratory distress syndrome. J Pathol. 199:496–508. 2003. View Article : Google Scholar : PubMed/NCBI
44	Norman J, Franz M, Messina J, Riker A, Fabri PJ, Rosemurgy AS and Gower WR Jr: Interleukin-1 receptor antagonist decreases severity of experimental acute pancreatitis. Surgery. 117:648–655. 1995. View Article : Google Scholar : PubMed/NCBI
45	Hughes CB, Grewal HP, Gaber LW, Kotb M, El-din AB, Mann L and Gaber AO: Anti-TNFalpha therapy improves survival and ameliorates the pathophysiologic sequelae in acute pancreatitis in the rat. Am J Surg. 171:274–280. 1996. View Article : Google Scholar : PubMed/NCBI
46	Baker SJ and Reddy EP: Transducers of life and death: TNF receptor superfamily and associated proteins. Oncogene. 12:1–9. 1996.PubMed/NCBI
47	Papachristou GI: Prediction of severe acute pancreatitis: Current knowledge and novel insights. World J Gastroenterol. 14:6273–6275. 2008. View Article : Google Scholar : PubMed/NCBI
48	Lukacs NW and Ward PA: Inflammatory mediators, cytokines, and adhesion molecules in pulmonary inflammation and injury. Adv Immunol. 62:257–304. 1996. View Article : Google Scholar : PubMed/NCBI
49	Chen C, Xu S, Wang WX, Ding YM, Yu KH, Wang B and Chen XY: Rosiglitazone attenuates the severity of sodium taurocholate-induced acute pancreatitis and pancreatitis-associated lung injury. Arch Med Res. 40:79–88. 2009. View Article : Google Scholar : PubMed/NCBI
50	Twait E, Williard DE and Samuel I: Dominant negative p38 mitogen-activated protein kinase expression inhibits NF-kappaB activation in AR42J cells. Pancreatology. 10:119–128. 2010. View Article : Google Scholar : PubMed/NCBI
51	Lv W, Lv C, Yu S, Yang Y, Kong H, Xie J, Sun H, Andersson R, Xu D, Chen B and Zhou M: Lipoxin A4 attenuation of endothelial inflammation response mimicking pancreatitis-induced lung injury. Exp Biol Med (Maywood). 238:1388–1395. 2013. View Article : Google Scholar : PubMed/NCBI
52	Chen P, Zhang Y, Qiao M and Yuan Y: Activated protein C, an anticoagulant polypeptide, ameliorates severe acute pancreatitis via regulation of mitogen-activated protein kinases. J Gastroenterol. 42:887–896. 2007. View Article : Google Scholar : PubMed/NCBI
53	Zhong H, SuYang H, Erdjument-Bromage H, Tempst P and Ghosh S: The transcriptional activity of NF-kappaB is regulated by the IkappaB-associated PKAc subunit through a cyclic AMP-independent mechanism. Cell. 89:413–424. 1997. View Article : Google Scholar : PubMed/NCBI
54	Yubero S, Ramudo L, Manso MA and De Dios I: Mechanisms of dexamethasone-mediated chemokine down-regulation in mild and severe acute pancreatitis. Biochim Biophys Acta. 1792:1205–1211. 2009. View Article : Google Scholar : PubMed/NCBI
55	Kim C, Sano Y, Todorova K, Carlson BA, Arpa L, Celada A, Lawrence T, Otsu K, Brissette JL, Arthur JS and Park JM: The kinase p38 alpha serves cell type-specific inflammatory functions in skin injury and coordinates pro- and anti-inflammatory gene expression. Nat Immunol. 9:1019–1027. 2008. View Article : Google Scholar : PubMed/NCBI