Melatonin attenuated inflammatory reaction by inhibiting the activation of p38 and NF‑κB in taurocholate‑induced acute pancreatitis

Chen,Yina; Zhao,Qian; Chen,Qinfen; Zhang,Yuxue; Shao,Bule; Jin,Yin; Wu,Jiansheng

doi:10.3892/mmr.2018.8614

Melatonin attenuated inflammatory reaction by inhibiting the activation of p38 and NF‑κB in taurocholate‑induced acute pancreatitis

Authors:
- Yina Chen
- Qian Zhao
- Qinfen Chen
- Yuxue Zhang
- Bule Shao
- Yin Jin
- Jiansheng Wu
View Affiliations

Affiliations: Department of Gastroenterology, Yuyao People's Hospital of Zhejiang Province, Yuyao, Zhejiang 315400, P.R. China, Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310000, P.R. China, Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
Published online on: February 16, 2018 https://doi.org/10.3892/mmr.2018.8614
Pages: 5934-5939

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

The aim of the present study was to investigate the protective mechanism underlying of melatonin in severe acute pancreatitis (SAP). A total of 64 male Sprague‑Dawley rats were randomly divided into four groups: The sham operation (SO) group, SAP group, melatonin treatment (MLT) group and p38 inhibitor (SB203580) treatment (SB) group. Acute pancreatitis was induced by 5% taurocholate through retrograde infusion into the biliopancreatic ducts. The melatonin and SB203580 treatment groups were administered with MLT and SB 30 min before operation the induction of SAP. Rats in each group were euthanized at 6 and 12 h following SAP induction. Blood and pancreatic tissues were removed for inflammatory examination. Peripheral blood mononuclear cells (PBMCs) were isolated following sacrifice to measure the phosphorylation of p38 and nuclear factor‑κB (NF‑κB was measured as p65 and phosphorylation of p65). The pretreatment of melatonin significantly attenuated the severity of pancreatitis. In addition, melatonin also reduced serum amylase and proinflammatory cytokine levels, including tumor necrosis factor‑α, interleukin (IL)‑1 and IL‑6. The mean pathological scores for pancreatic tissues in the MLT group were higher than those for samples in the SO group, but were lower than those for samples in the SAP group at each time-point. Phosphorylation of p38 and p65 levels in the melatonin treatment group were lower than that in the SAP group, and higher in the SAP group than in the SO group, and the SB203580 treatment group. Furthermore, melatonin significantly inhibited the activation of p38 and NF‑κB in PBMCs. The authors revealed that melatonin may attenuate inflammatory reactions by inhibiting the activation of p38 MAPK and NF‑κB in both acute pancreatitis rats and PBMCs. SAP is a severe disease with a high risk of morbidity and mortality. It is important to attenuated inflammatory reaction in acute pancreatitis. Thus, the authors studied melatonin, which is synthesized by the pineal gland and released into the blood. Previous studies have shown that melatonin serves a protective role in the early course of human acute pancreatitis, and melatonin concentration variations are closely related to the severity of acute pancreatitis. It may be concluded that melatonin may attenuates inflammatory reactions by inhibiting the activation of p38 MAPK and NF‑κB in both acute pancreatitis rats and PBMCs.

View Figures

View References

1	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
2	Norman J: The role of cytokines in the pathogenesis of acute pancreatitis. Am J Surg. 175:76–83. 1998. View Article : Google Scholar : PubMed/NCBI
3	Büchler MW, Gloor B, Müller CA, Friess H, Seiler CA and Uhl W: Acute necrotizing pancreatitis: Treatment strategy according to the status of infection. Ann Surg. 232:619–626. 2000. View Article : Google Scholar : PubMed/NCBI
4	Xiao WQ, Yin GJ, Fan YT, Qiu L, Cang XF, Yu G, Hu YL, Xing M, Wu DQ, Wang XP, et al: Catalpol ameliorates sodium taurocholate-induced acute pancreatitis in rats via inhibiting activation of nuclear factor kappa B. Int J Mol Sci. 15:11957–11972. 2014. View Article : Google Scholar : PubMed/NCBI
5	Wei S, Huang Q, Li J, Liu Z, You H, Chen Y and Gong J: Taurine attenuates liver injury by downregulating phosphorylated p38 MAPK of Kupffer cells in rats with severe acute pancreatitis. Inflammation. 35:690–701. 2012. View Article : Google Scholar : PubMed/NCBI
6	Liu HS, Pan CE, Liu QG, Yang W and Liu XM: Effect of NF-kappaB and p38 MAPK in activated monocytes/macrophages on pro-inflammatory cytokines of rats with acute pancreatitis. World J Gastroenterol. 9:2513–2518. 2003. View Article : Google Scholar : PubMed/NCBI
7	Pagès G, Lenormand P, L'Allemain G, Chambard JC, Meloche S and Pouysségur J: Mitogen-activated protein kinases p42mapk and p44mapk are required for fibroblast proliferation. Proc Natl Acad Sci USA. 90:pp. 8319–8323. 1993; View Article : Google Scholar : PubMed/NCBI
8	Li Q and Verma IM: NF-kappaB regulation in the immune system. Nat Rev Immunol. 2:725–734. 2002. View Article : Google Scholar : PubMed/NCBI
9	Lerner AB, Case JD and Takahashi Y: Isolation of melatonin and 5-methoxyindole-3-acetic acid from bovine pineal glands. J Biol Chem. 235:1992–1997. 1960.PubMed/NCBI
10	Berger J: A two-clock model of circadian timing in the immune system of mammals. Pathol Biol (Paris). 56:286–291. 2008. View Article : Google Scholar : PubMed/NCBI
11	Galano A, Tan DX and Reiter RJ: Melatonin as a natural ally against oxidative stress: A physicochemical examination. J Pineal Res. 51:1–16. 2011. View Article : Google Scholar : PubMed/NCBI
12	García JJ, Reiter RJ, Pié J, Ortiz GG, Cabrera J, Sáinz RM and Acuña-Castroviejo D: Role of pinoline and melatonin in stabilizing hepatic microsomal membranes against oxidative stress. J Bioenerg Biomembr. 31:609–616. 1999. View Article : Google Scholar : PubMed/NCBI
13	Chen CF, Wang D, Reiter RJ and Yeh DY: Oral melatonin attenuates lung inflammation and airway hyperreactivity induced by inhalation of aerosolized pancreatic fluid in rats. J Pineal Res. 50:46–53. 2011. View Article : Google Scholar : PubMed/NCBI
14	Motilva V, García-Mauriño S, Talero E and Illanes M: New paradigms in chronic intestinal inflammation and colon cancer: Role of melatonin. J Pineal Res. 51:44–60. 2011. View Article : Google Scholar : PubMed/NCBI
15	Jung KH, Hong SW, Zheng HM, Lee DH and Hong SS: Melatonin downregulates nuclear erythroid 2-related factor 2 and nuclear factor-kappaB during prevention of oxidative liver injury in a dimethylnitrosamine model. J Pineal Res. 47:173–183. 2009. View Article : Google Scholar : PubMed/NCBI
16	Jung KH, Hong SW, Zheng HM, Lee HS, Lee H, Lee DH, Lee SY and Hong SS: Melatonin ameliorates cerulein-induced pancreatitis by the modulation of nuclear erythroid 2-related factor 2 and nuclear factor-kappaB in rats. J Pineal Res. 48:239–250. 2010. View Article : Google Scholar : PubMed/NCBI
17	Pereda J, Sabater L, Aparisi L, Escobar J, Sandoval J, Viña J, López-Rodas G and Sastre J: Interaction between cytokines and oxidative stress in acute pancreatitis. Curr Med Chem. 13:2775–2787. 2006. View Article : Google Scholar : PubMed/NCBI
18	Xue DB, Zhang WH, Yun XG, Song C, Zheng B, Shi XY and Wang HY: Regulating effects of arsenic trioxide on cell death pathways and inflammatory reactions of pancreatic acinar cells in rats. Chin Med J (Engl). 120:690–695. 2007.PubMed/NCBI
19	Pedreira PR, García-Prieto E, Parra D, Astudillo A, Diaz E, Taboada F and Albaiceta GM: Effects of melatonin in an experimental model of ventilator-induced lung injury. Am J Physiol Lung Cell Mol Physiol. 295:L820–L827. 2008. View Article : Google Scholar : PubMed/NCBI
20	Tanaka T, Yasui Y, Tanaka M, Tanaka T, Oyama T and Rahman KM: Melatonin suppresses AOM/DSS-induced large bowel oncogenesis in rats. Chem Biol Interact. 177:128–136. 2009. View Article : Google Scholar : PubMed/NCBI
21	Torres M and Forman HJ: Redox signaling and the MAP kinase pathways. Biofactors. 17:287–296. 2003. View Article : Google Scholar : PubMed/NCBI
22	Viatour P, Merville MP, Bours V and Chariot A: Phosphorylation of NF-kappaB and IkappaB proteins: Implications in cancer and inflammation. Trends Biochem Sci. 30:43–52. 2005. View Article : Google Scholar : PubMed/NCBI
23	Wang X, Martindale JL, Liu Y and Holbrook NJ: The cellular response to oxidative stress: Influences of mitogen-activated protein kinase signalling pathways on cell survival. Biochem J. 333:291–300. 1998. View Article : Google Scholar : PubMed/NCBI
24	Blinman TA, Gukovsky I, Mouria M, Zaninovic V, Livingston E, Pandol SJ and Gukovskaya AS: Activation of pancreatic acinar cells on isolation from tissue: Cytokine upregulation via p38 MAP kinase. Am J Physiol Cell Physiol. 279:C1993–C2003. 2000. View Article : Google Scholar : PubMed/NCBI
25	Choi SB, Bae GS, Jo IJ, Seo SH, Kim DG, Shin JY, Hong SH, Choi BM, Park SH, Song HJ and Park SJ: Protective effects of lithospermum erythrorhizon against cerulein-induced acute pancreatitis. Pancreas. 44:31–40. 2015. View Article : Google Scholar : PubMed/NCBI
26	Kim TH, Bae GS, Oh HJ, Kim MS, Park KC, Koo BS, Kim BJ, Yang YS, Park DE, Lee JH, et al: 2′,4′,6′-Tris(methoxymethoxy) chalcone (TMMC) attenuates the severity of cerulein-induced acute pancreatitis and associated lung injury. Am J Physiol Gastrointest Liver Physiol. 301:G694–G706. 2011. View Article : Google Scholar : PubMed/NCBI
27	Bae GS, Kim MS, Jeong J, Lee HY, Park KC, Koo BS, Kim BJ, Kim TH, Lee SH, Hwang SY, et al: Piperine ameliorates the severity of cerulein-induced acute pancreatitis by inhibiting the activation of mitogen activated protein kinases. Biochem Biophys Res Commun. 410:382–388. 2011. View Article : Google Scholar : PubMed/NCBI
28	Zhang S, Li W, Gao Q and Wei T: Effect of melatonin on the generation of nitric oxide in murine macrophages. Eur J Pharmacol. 501:25–30. 2004. View Article : Google Scholar : PubMed/NCBI
29	Aparicio-Soto M, Alarcón-de-la-Lastra C, Cárdeno A, Sánchez-Fidalgo S and Sanchez-Hidalgo M: Melatonin modulates microsomal PGE synthase 1 and NF-E2-related factor-2-regulated antioxidant enzyme expression in LPS-induced murine peritoneal macrophages. Br J Pharmacol. 171:134–144. 2014. View Article : Google Scholar : PubMed/NCBI
30	Jung KH, Hong SW, Zheng HM, Lee HS, Lee H, Lee DH, Lee SY and Hong SS: Melatonin ameliorates cerulein-induced pancreatitis by the modulation of nuclear erythroid 2-related factor 2 and nuclear factor-kappaB in rats. J Pineal Res. 48:239–250. 2010. View Article : Google Scholar : PubMed/NCBI