Current opinion in gastroenterology · 2009
Nuclear factor-kappa B in intestinal protection and destruction.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАОбзорНазвание и аннотация: Перевод пока не подготовлен
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Spehlmann Martina E, Eckmann Lars
Аннотация
PURPOSE OF REVIEW: Nuclear factor-kappa B (NF-kappaB) is a key transcriptional regulator of innate and adaptive immunity. This review highlights new insights into the functions of NF-kappaB in normal homeostasis and specific disease processes in the intestinal tract.
RECENT FINDINGS: Inflammatory bowel disease and experimental intestinal inflammation are characterized by NF-kappaB activation and increased expression of proinflammatory NF-kappaB target genes. Accordingly, NF-kappaB inhibition protects against chronic intestinal inflammation and necrotizing enterocolitis in animal models. However, recent findings suggest that NF-kappaB has not only proinflammatory but also tissue-protective functions. Thus, genetic ablation of the regulatory subunit, IkappaB kinase (IKK)gamma, of the central kinase complex required for NF-kappaB activation, IKK, or of both kinase subunits, IKKalpha and IKKbeta, in intestinal epithelial cells causes spontaneous murine colitis. Pharmacological inhibition of IKKbeta, and loss of IKKbeta or NF-kappaB p65 in the epithelium, sensitizes mice to acute inflammatory and injurious challenges. Deficiency in Toll-like receptor 5, a strong activator of NF-kappaB, results in spontaneous colitis and exacerbates mucosal inflammatory responses to Salmonella infection. Conversely, Toll-like receptor 5 stimulation confers radioprotection in the intestine.
SUMMARY: NF-kappaB has multiple, often opposing functions in the intestine. Antiapoptotic actions of NF-kappaB in intestinal epithelial cells dominate tissue responses to many acute inflammatory and injurious challenges, whereas proinflammatory and cell survival functions of NF-kappaB in macrophages and T cells govern chronic intestinal inflammation.
RECENT FINDINGS: Inflammatory bowel disease and experimental intestinal inflammation are characterized by NF-kappaB activation and increased expression of proinflammatory NF-kappaB target genes. Accordingly, NF-kappaB inhibition protects against chronic intestinal inflammation and necrotizing enterocolitis in animal models. However, recent findings suggest that NF-kappaB has not only proinflammatory but also tissue-protective functions. Thus, genetic ablation of the regulatory subunit, IkappaB kinase (IKK)gamma, of the central kinase complex required for NF-kappaB activation, IKK, or of both kinase subunits, IKKalpha and IKKbeta, in intestinal epithelial cells causes spontaneous murine colitis. Pharmacological inhibition of IKKbeta, and loss of IKKbeta or NF-kappaB p65 in the epithelium, sensitizes mice to acute inflammatory and injurious challenges. Deficiency in Toll-like receptor 5, a strong activator of NF-kappaB, results in spontaneous colitis and exacerbates mucosal inflammatory responses to Salmonella infection. Conversely, Toll-like receptor 5 stimulation confers radioprotection in the intestine.
SUMMARY: NF-kappaB has multiple, often opposing functions in the intestine. Antiapoptotic actions of NF-kappaB in intestinal epithelial cells dominate tissue responses to many acute inflammatory and injurious challenges, whereas proinflammatory and cell survival functions of NF-kappaB in macrophages and T cells govern chronic intestinal inflammation.