NLRP3炎性小体与急性胰腺炎的研究进展
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摘要
目的探讨NLRP3炎性小体与急性胰腺炎病情的发展,以及与急性胰腺炎导致的胰腺原位和胰腺外损伤的关系。方法对近年来国内外有关NLRP3炎性小体与急性胰腺炎病情发展,胰腺原位和胰腺外脏器损伤研究的相关文献进行综述。结果急性胰腺炎发生时,NLRP3炎性小体激活参与了急性胰腺炎时各脏器的损伤,NLRP3炎性小体激活越多,对机体的损伤越严重,通过对NLRP3炎性小体激活机制的调节,可以减少NLRP3炎性小体的激活,并最终减轻各脏器的损伤。结论 NLRP3炎性小体的激活参与了急性胰腺炎的进程,但仍需进一步临床研究予以验证。
Objective To investigate relationship between nod-like-receptor protein 3(NLRP3) inflammasome and acute pancreatitis induced pancreas and extrapancreatic organs injury. Method The related literatures on the relationship between the nod-like-receptor protein 1 inflammasome(NLRP3 inflammasome) and the acute pancreatitis in recent years were reviewed. Results The activation and regulation of NLRP3 inflammatory corpuscle are involved in the injury of various organs in acute pancreatitis. The more the activation of NLRP3 inflammatory corpuscle, the more severe the damage to the body. Through the regulation of the activation mechanism of NLRP3 inflammatory corpuscle, the activation of NLRP3 inflammatory corpuscle can be reduced, and finally the injury of various organs can be reduced.Conclusion The activation of NLRP3 inflammatory corpuscle is involved in the process of acute pancreatitis, but it still needs to be verified by further clinical studies.
Objective To investigate relationship between nod-like-receptor protein 3(NLRP3) inflammasome and acute pancreatitis induced pancreas and extrapancreatic organs injury. Method The related literatures on the relationship between the nod-like-receptor protein 1 inflammasome(NLRP3 inflammasome) and the acute pancreatitis in recent years were reviewed. Results The activation and regulation of NLRP3 inflammatory corpuscle are involved in the injury of various organs in acute pancreatitis. The more the activation of NLRP3 inflammatory corpuscle, the more severe the damage to the body. Through the regulation of the activation mechanism of NLRP3 inflammatory corpuscle, the activation of NLRP3 inflammatory corpuscle can be reduced, and finally the injury of various organs can be reduced.Conclusion The activation of NLRP3 inflammatory corpuscle is involved in the process of acute pancreatitis, but it still needs to be verified by further clinical studies.
引文
1 Coll RC, Holley CL, Schroder K. Mitochondrial DNA synthesis fuels NLRP3 inflammasome. Cell Res, 2018, 28(11):1046-1047.
2 Qiu H, Liu W, Lan T, et al. Salvianolate reduces atrial fibrillation through suppressing atrial interstitial fibrosis by inhibiting TGFbetal/Smad2/3 and TXNIP/NLRP3 inflammasome signaling pathways in post-MI rats. Phytomedicine, 2018, 51:255-265.
3 Mao L, Kitani A, StroberW, et al.The role of NLRP3 and IL-lbeta in the pathogenesis of inflammatory bowel disease. Front Immunol, 2018, 9:2566.
4 Gutierrez Lopez J, Licata J, Pypker T, et al. Effects of heater wattage on sap flux density estimates using an improved tree-cut experiment. Tree Physiol, 2018 Dec 31.[Epub ahead of print].
5 Elliott EI, Sutterwala FS. Initiation and perpetuation of NLRP3inflammasome activation and assembly. Immunol Rev, 2015,265(1):35-52.
6 Song N, Li T. Regulation of NLRP3 inflammasome by phosphorylation. Front Immunol, 2018, 9:2305.
7 Hoss F, Rodriguez-Alcazar JF, Latz E. Assembly and regulation of ASC specks. Cell Mol Life Sci, 2017, 74(7):1211-1229.
8 Shao BZ, Xu ZQ, Han BZ, et al. NLRP3 inflammasome and its inhibitors:a review. Front Pharmacol, 2015, 6:262.
9 Artlett CM, Thacker JD. Molecular activation of the NLRP3inflammasome in fibrosis:common threads linking divergent fibrogenic diseases. Antioxid Redox Signal, 2015, 22(13):1162-1175.
10 Ren JD, Ma J, Hou J, et al. Hydrogen-rich saline inhibits NLRP3inflammasome activation and attenuates experimental acute pancreatitis in mice. Mediators Inflamm, 2014, 2014:930894.
11 Perregaux D, Gabel CA. Interleukin-1 beta maturation and release in response to ATP and nigericin. Evidence that potassium depletion mediated by these agents is a necessary and common feature of their activity. J Biol Chem, 1994, 269(21):15195-15203.
12 Wang S, Yuan YH, Chen NH, et al. The mechanisms of NLRP3inflammasome/pyroptosis activation and their role in Parkinson's disease. Int Immunopharmacol, 2019, 67:458-464.
13 Sho T, Xu J. Role and mechanism of ROS scavengers in alleviating NLRP3-mediated inflammation. Biotechnol Appl Biochem, 2019,66(1):4-13.
14 Bordt EA, Polster BM. NADPH oxidase-and mitochondriaderived reactive oxygen species in proinflammatory microglial activation:a bipartisan affair? Free Radic Biol Med, 2014, 76:34-46.
15 Man SM, Place DE, Kuriakose T, et al. Interferon-inducible guanylate-binding proteins at the interface of cell-autonomous immunity and inflammasome activation. J Leukoc Biol, 2017,101(1):143-150.
16 Yang J, Zhao Y, Shao F. Non-canonical activation of inflammatory caspases by cytosolic LPS in innate immunity. Curr Opin Immunol, 2015, 32:78-83.
17 Gaidt MM, Ebert TS, Chauhan D, et al.Human monocytes engage an alternative inflammasome pathway. Immunity, 2016, 44(4):833-846.
18 Lu B, Nakamura T, Inouye K, et al. Novel role of PKR in inflammasome activation and HMGB1 release. Nature, 2012,488(7413):670-674.
19 He Y, Franchi L, Nunez G. The protein kinase PKR is critical for LPS-induced iNOS production but dispensable for inflammasome activation in macrophages. Eur J Immunol, 2013,43(5):1147-1152.
20 Shenoy AR, Wellington DA, Kumar P, et al. MacMicking, GBP5promotes NLRP3 inflammasome assembly and immunity in mammals. Science, 2012, 336(6080):481-485.
21 Meunier E, Dick MS, Dreier RF, et al. Caspase-11 activation requires lysis of pathogen-containing vacuoles by IFN-induced GTPases. Nature, 2014, 509(7500):366-370.
22 Shi H, Wang Y, Li X, et al. NLRP3 activation and mitosis are mutually exclusive events coordinated by NEK7, a new inflammasome component. Nat Immunol, 2016,17(3):250-258.
23 Schmid-Burgk JL, Chauhan D, Schmidt T, et al. A Genome-wide CRISPR(clustered regularly interspaced short palindromic repeats)screen identifies NEK7 as an essential component of NLRP3 inflammasome activation. J Biol Chem, 2016, 291(1):103-109.
24 He Y, Zeng MY, Yang D, et al. NEK7 is an essential mediator of NLRP3 activation downstream of potassium efflux. Nature, 2016,530(7590):354-357.
25 Fry AM, O'Regan L, Sabir SR, et al. Cell cycle regulation by the NEK family of protein kinases. J Cell Sci, 2012, 125((Pt 19):4423-4433.
26 Kanak MA, Shahbazov R, Yoshimatsu G, et al. A small molecule inhibitor of NFkappaB blocks ER stress and the NLRP3inflammasome and prevents progression of pancreatitis. J Gastroenterol, 2017,52(3):352-365.
27 Aruna R, Geetha A, Suguna P. Rutin modulates ASC expression in NLRP3 inflammasome:a study in alcohol and cerulein-induced rat model of pancreatitis. Mol Cell Biochem, 2014, 396(1-2):269-280.
28尤运冬,赵亮,梅方超,等.巨噬细胞移动抑制因子抑制剂ISO-1在妊娠大鼠急性坏死性胰腺炎肠损伤中的作用.中国普外基础与临床杂志,2018, 25(11):1308-1312.
29武永胜,李得溪,赵海平,等.银杏叶提取物对重症急性胰腺炎大鼠脑组织中IL-1β、IL-6和TNF-a表达水平的影响.中国普外基础与临床杂志,2012, 19(6):616-621.
30 Hoque R, Sohail M, Malik A, et al. TLR9 and the NLRP3inflammasome link acinar cell death with inflammation in acute pancreatitis. Gastroenterology, 2011,141(1):358-369.
31 York JM, Castellanos KJ, Cabay RJ, et al. Inhibition of the nucleotide-binding domain, leucine-rich containing family, pyrindomain containing 3 inflammasome reduces the severity of experimentally induced acute pancreatitis in obese mice. Transl Res, 2014, 164(4):259-269.
32 Dong Z, Shang H, Chen YQ, et al. Sulforaphane protects pancreaticacinar cell injury by modulating Nrf2-mediated oxidative stress and NLRP3 inflammatory pathway. Oxid Med Cell Longev, 2016,2016:7864150.
33 Jakkampudi A, Jangala R, Reddy R, et al. Acinar injury and early cytokine response in human acute biliary pancreatitis. Sci Rep,2017, 7(1):15276.
34 Yu J, Ni L, Zhang X, et al. Surfactant protein D dampens lung injury by suppressing NLRP3 inflammasome activation and NFkappaB signaling in acute pancreatitis. Shock,(2018).
35 Xu S, Wei S, Guo Y, et al. Involvement of nucleotide-binding and oligomerization domain-like receptors in the intestinal injury of severe acute pancreatitis in rats. Pancreas, 2018,47(2):245-251.
2 Qiu H, Liu W, Lan T, et al. Salvianolate reduces atrial fibrillation through suppressing atrial interstitial fibrosis by inhibiting TGFbetal/Smad2/3 and TXNIP/NLRP3 inflammasome signaling pathways in post-MI rats. Phytomedicine, 2018, 51:255-265.
3 Mao L, Kitani A, StroberW, et al.The role of NLRP3 and IL-lbeta in the pathogenesis of inflammatory bowel disease. Front Immunol, 2018, 9:2566.
4 Gutierrez Lopez J, Licata J, Pypker T, et al. Effects of heater wattage on sap flux density estimates using an improved tree-cut experiment. Tree Physiol, 2018 Dec 31.[Epub ahead of print].
5 Elliott EI, Sutterwala FS. Initiation and perpetuation of NLRP3inflammasome activation and assembly. Immunol Rev, 2015,265(1):35-52.
6 Song N, Li T. Regulation of NLRP3 inflammasome by phosphorylation. Front Immunol, 2018, 9:2305.
7 Hoss F, Rodriguez-Alcazar JF, Latz E. Assembly and regulation of ASC specks. Cell Mol Life Sci, 2017, 74(7):1211-1229.
8 Shao BZ, Xu ZQ, Han BZ, et al. NLRP3 inflammasome and its inhibitors:a review. Front Pharmacol, 2015, 6:262.
9 Artlett CM, Thacker JD. Molecular activation of the NLRP3inflammasome in fibrosis:common threads linking divergent fibrogenic diseases. Antioxid Redox Signal, 2015, 22(13):1162-1175.
10 Ren JD, Ma J, Hou J, et al. Hydrogen-rich saline inhibits NLRP3inflammasome activation and attenuates experimental acute pancreatitis in mice. Mediators Inflamm, 2014, 2014:930894.
11 Perregaux D, Gabel CA. Interleukin-1 beta maturation and release in response to ATP and nigericin. Evidence that potassium depletion mediated by these agents is a necessary and common feature of their activity. J Biol Chem, 1994, 269(21):15195-15203.
12 Wang S, Yuan YH, Chen NH, et al. The mechanisms of NLRP3inflammasome/pyroptosis activation and their role in Parkinson's disease. Int Immunopharmacol, 2019, 67:458-464.
13 Sho T, Xu J. Role and mechanism of ROS scavengers in alleviating NLRP3-mediated inflammation. Biotechnol Appl Biochem, 2019,66(1):4-13.
14 Bordt EA, Polster BM. NADPH oxidase-and mitochondriaderived reactive oxygen species in proinflammatory microglial activation:a bipartisan affair? Free Radic Biol Med, 2014, 76:34-46.
15 Man SM, Place DE, Kuriakose T, et al. Interferon-inducible guanylate-binding proteins at the interface of cell-autonomous immunity and inflammasome activation. J Leukoc Biol, 2017,101(1):143-150.
16 Yang J, Zhao Y, Shao F. Non-canonical activation of inflammatory caspases by cytosolic LPS in innate immunity. Curr Opin Immunol, 2015, 32:78-83.
17 Gaidt MM, Ebert TS, Chauhan D, et al.Human monocytes engage an alternative inflammasome pathway. Immunity, 2016, 44(4):833-846.
18 Lu B, Nakamura T, Inouye K, et al. Novel role of PKR in inflammasome activation and HMGB1 release. Nature, 2012,488(7413):670-674.
19 He Y, Franchi L, Nunez G. The protein kinase PKR is critical for LPS-induced iNOS production but dispensable for inflammasome activation in macrophages. Eur J Immunol, 2013,43(5):1147-1152.
20 Shenoy AR, Wellington DA, Kumar P, et al. MacMicking, GBP5promotes NLRP3 inflammasome assembly and immunity in mammals. Science, 2012, 336(6080):481-485.
21 Meunier E, Dick MS, Dreier RF, et al. Caspase-11 activation requires lysis of pathogen-containing vacuoles by IFN-induced GTPases. Nature, 2014, 509(7500):366-370.
22 Shi H, Wang Y, Li X, et al. NLRP3 activation and mitosis are mutually exclusive events coordinated by NEK7, a new inflammasome component. Nat Immunol, 2016,17(3):250-258.
23 Schmid-Burgk JL, Chauhan D, Schmidt T, et al. A Genome-wide CRISPR(clustered regularly interspaced short palindromic repeats)screen identifies NEK7 as an essential component of NLRP3 inflammasome activation. J Biol Chem, 2016, 291(1):103-109.
24 He Y, Zeng MY, Yang D, et al. NEK7 is an essential mediator of NLRP3 activation downstream of potassium efflux. Nature, 2016,530(7590):354-357.
25 Fry AM, O'Regan L, Sabir SR, et al. Cell cycle regulation by the NEK family of protein kinases. J Cell Sci, 2012, 125((Pt 19):4423-4433.
26 Kanak MA, Shahbazov R, Yoshimatsu G, et al. A small molecule inhibitor of NFkappaB blocks ER stress and the NLRP3inflammasome and prevents progression of pancreatitis. J Gastroenterol, 2017,52(3):352-365.
27 Aruna R, Geetha A, Suguna P. Rutin modulates ASC expression in NLRP3 inflammasome:a study in alcohol and cerulein-induced rat model of pancreatitis. Mol Cell Biochem, 2014, 396(1-2):269-280.
28尤运冬,赵亮,梅方超,等.巨噬细胞移动抑制因子抑制剂ISO-1在妊娠大鼠急性坏死性胰腺炎肠损伤中的作用.中国普外基础与临床杂志,2018, 25(11):1308-1312.
29武永胜,李得溪,赵海平,等.银杏叶提取物对重症急性胰腺炎大鼠脑组织中IL-1β、IL-6和TNF-a表达水平的影响.中国普外基础与临床杂志,2012, 19(6):616-621.
30 Hoque R, Sohail M, Malik A, et al. TLR9 and the NLRP3inflammasome link acinar cell death with inflammation in acute pancreatitis. Gastroenterology, 2011,141(1):358-369.
31 York JM, Castellanos KJ, Cabay RJ, et al. Inhibition of the nucleotide-binding domain, leucine-rich containing family, pyrindomain containing 3 inflammasome reduces the severity of experimentally induced acute pancreatitis in obese mice. Transl Res, 2014, 164(4):259-269.
32 Dong Z, Shang H, Chen YQ, et al. Sulforaphane protects pancreaticacinar cell injury by modulating Nrf2-mediated oxidative stress and NLRP3 inflammatory pathway. Oxid Med Cell Longev, 2016,2016:7864150.
33 Jakkampudi A, Jangala R, Reddy R, et al. Acinar injury and early cytokine response in human acute biliary pancreatitis. Sci Rep,2017, 7(1):15276.
34 Yu J, Ni L, Zhang X, et al. Surfactant protein D dampens lung injury by suppressing NLRP3 inflammasome activation and NFkappaB signaling in acute pancreatitis. Shock,(2018).
35 Xu S, Wei S, Guo Y, et al. Involvement of nucleotide-binding and oligomerization domain-like receptors in the intestinal injury of severe acute pancreatitis in rats. Pancreas, 2018,47(2):245-251.