Chronic colitis induces expression of beta-defensins in murine intestinal epithelial cells

作者：Rahman A; Fahlgren A; Sundstedt C; Hammarstrom S; Danielsson A; Hammarstrom M L^*

来源：Clinical and Experimental Immunology, 2011, 163(1): 123-130.

DOI：10.1111/j.1365-2249.2010.04282.x

• acute and chronic DSS-induced colitis
• anti-microbial peptides
• colonic epithelium
• IL-2-
• - mice
• interleukin-17

P>Anti-microbial peptides are important effectors in innate immunity. In the gut they defend against pathogens, shape the commensal microbiota and probably control intestinal homeostasis. Ulcerative colitis (UC), but not Crohn's disease, shows increased expression of inducible beta-defensins (hBD-2, hBD-3 and hBD-4) in colonic epithelial cells. Does inducible defensin production precede the chronic intestinal inflammation characteristic of UC, or is it a consequence of the T cell-driven chronic inflammation? The aim was to analyse defensin mRNA and protein expression in colonic epithelial cells in two colitis mouse models resembling UC, the interleukin (IL)-2-/- mouse and the dextran sulphate sodium (DSS)-induced colitis mouse. Defensin mRNA was assayed by in situ hybridization and quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR). Defensin peptide was assayed by immunohistochemistry. Mouse beta-defensin 3 (mBD-3, orthologue to hBD-2) was up-regulated strongly in colonic epithelium of 15-week-old IL-2-/- mice and DSS-induced colitis mice with chronic bowel inflammation, but not in apparently healthy IL-2-/- 5-week-old mice, IL-2+/- 15-week-old mice or in acute stage DSS mice. Up-regulation was seen both at the mRNA- and at the protein level (only mBD-3 investigated). IL-17, but not several other cytokines, including interferon (IFN)-gamma, induced mBD-3 mRNA expression in mouse colon carcinoma cells. The mRNA expression level of the constitutively expressed alpha-defensin, cryptdin-4, was up-regulated marginally in acute stage DSS-colitis mice and in IL-2-/- mice before signs of colitis. Inducible beta-defensin expression in colonic epithelium is the consequence of the chronic bowel inflammation caused by activated T cells releasing cytokines including IL-17.

• 出版日期2011-1