摘要
<正>克罗恩病(Crohn,CD)和溃疡性结肠炎(ulcercolitis,UC)是炎症性肠病(inflammatory bowel dis-ease,IBD)的常见表现形式,病理特征为慢性非特异性肠道炎症。IBD病因与感染、遗传易感性、免疫紊乱和菌群失调等有关,但具体病因尚不明确[1]。过度炎症是IBD病理生理学最突出的特征,而转录因子核因子κB(nuclear factor kappa B,NF-κB)信号通路失调通常导致过度炎症。文章总结了经典和非经典NF-κB通路在IBD中的作用机
引文
[1]孙利,李一帆.儿童炎症性肠病与免疫缺陷[J].中国实用儿科杂志,2018,33(1):37-41.
[2]Gilmore TD.Introduction to NF-kappaB:players,pathways,perspectives[J].Oncogene,2006,25(51):6680-6684.
[3]Brown KD,Claudio E,Siebenlist U.The roles of the classical and alternative nuclear factor-kappaB pathways:potential implications for autoimmunity and rheumatoid arthritis[J].Arthritis Res Therapy,2008,10(4):212.
[4]Baud V,Karin M.Is NF-kappaB a good target for cancer therapy?Hopes and pitfalls[J].Nat Rev Drug Discov,2009,8(1):33-40.
[5]Sun SC.Controlling the fate of NIK:a central stage in noncanonical NF-kappaB signaling[J].Sci Signal,2010,3(123):pe18.
[6]Sun SC.The noncanonical NF-κB pathway[J].Immunol Rev,2012,246(1):125-140.
[7]Kanai T,Ilyama R,Ishikura T,et al.Role of the innate immune system in the development of chronic colitis[J].J Gastroenterol,2002,37(Suppl 14):38-42.
[8]Amin MR,Orenuga T,Tyagi S,et al.Tumor necrosis factor-αrepresses the expression of NHE2 through NF-κB activation in intestinal epithelial cell model,C2BBe1[J].Inflamm Bowel Dis,2015,17(3):720-731.
[9]Ye X,Sun M.AGR2 ameliorates tumor necrosis factor-α-induced epithelial barrier dysfunction via suppression of NF-κBp65-mediated MLCK/p-MLC pathway activation[J].Int J Mol Med,2017,39(5):1206-1214.
[10]Hausmann M,Kiessling S,Mestermann S,et al.Toll-like receptors 2 and 4 are up-regulated during intestinal inflammation[J].Gastroenterology,2002,122(7):1987-2000.
[11]Wei D,Jingjing Z,Aning S,et al.Protective effect of naringenin against experimental colitis via suppression of Toll-like receptor 4/NF-κB signalling[J].Br J Nutr,2013,110(4):599-608.
[12]Abbott DW,Yang Y,Hutti JE,et al.Coordinated regulation of Toll-like receptor and NOD2 signaling by K63-linked polyubiquitin chains[J].Mol Cell Biol,2007,27(17):6012-6025.
[13]Danese S,Scaldaferri F,Vetrano S,et al.Critical role of the CD40 CD40-ligand pathway in regulating mucosal inflammation-driven angiogenesis in inflammatory bowel disease[J].Gut,2007,56(9):1248-1256.
[14]Rescigno M.The intestinal epithelial barrier in the control of homeostasis and immunity[J].Trends Immunol,2011,32(6):256-264.
[15]Wang Y,Koroleva EP,Kruglov AA,et al.Lymphotoxin beta receptor signaling in intestinal epithelial cells orchestrates innate immune responses against mucosal bacterial infection[J].Immunity,2010,32(3):403-413.
[16]Tilg H,Moschen AR,Kaser A,et al.Gut,inflammation and osteoporosis:basic and clinical concepts[J].Gut,2008,57(5):684-694.
[17]Hollenbach E,Neumann M,Vieth M,et al.Inhibition of p38 MAPkinase-and RICK/NF-kappa B-signaling suppresses inflammatory bowel disease[J].FASEB J,2004,18(13):1550-1552.
[18]Dotan I,Werner L,Vigodman S,et al.CXCL12 is a constitutive and inflammatory chemokine in the intestinal immune system[J].Inflamm Bowel Dis,2010,16(4):583-592.
[19]Lich JD,Williams KL,Moore CB,et al.Monarch-1 suppresses non-canonical NF-kappaB activation and p52-dependent chemokine expression in monocytes[J].J Immunol,2007,178(3):1256-1260.
[20]Allen IC,Wilson JE,Schneider M,et al.NLRP12 suppresses colon inflammation and tumorigenesis through the negative regulation of noncanonical NF-κB signaling[J].Immunity,2012,36(5):742-754.
[21]Lalani AI,Moore CR,Luo C,et al.Myeloid cell TRAF3 regulates immune responses and inhibits inflammation and tumor development in mice[J].J Immunol,2015,194(1):334-348.
[22]Shen J,Qiao YQ,Ran ZH,et al.Up-regulation and pre-activation of TRAF3 and TRAF5 in inflammatory bowel disease[J].Int J Med Sci,2013,10(2):156-163.
[23]Grech AP,Amesbury M,Chan T,et al.TRAF2 differentially regulates the canonical and noncanonical pathways of NF-kappaBactivation in mature B cells[J].Immunity,2004,21(5):629-642.
[24]皮壮,王朝霞.2015 ESPGHAN《生物类似药在小儿炎症性肠病中的应用共识》解读[J].中国实用儿科杂志,2016,31(7):485-489.
[25]Peyrin-Biroulet L.Anti-TNF therapy in inflammatory bowel diseases:a huge review[J].Minerva Gastroenterol Dietol,2010,56(2):233-243.
