title: Interleukin-1beta targets interleukin-6 in progressing dextran sulfate sodium-induced experimental colitis.
abstract: Inflammatory bowel disease (IBD) is an immunologically mediated disorder that is characterized by chronic, relapsing, and inflammatory responses. Dextran sulfate sodium (DSS)-induced experimental colitis in mice has been recognized as a useful model for human IBD and interleukin (IL)-1beta is a key cytokine in the onset of IBD. The purpose of the present study was to clarify which pro-inflammatory mediators are targeted by IL-1beta in mice with DSS-induced colitis. First, we found that DSS markedly induced IL-1beta production in both dose- and time-dependent manners (P < 0.05 and P < 0.01, respectively) in murine peritoneal macrophages (pMphi), while that of tumor necrosis factor-alpha was insignificant. Further, the expressions of mRNA and protein for IL-1beta were increased in colonic mucosa and pMphi from mice that received drinking water containing 5% DSS for 7 days (P < 0.01, each). In addition, the expressions of IL-6, granulocyte macrophage-colony stimulating factor, inducible nitric oxide synthase, and cyclooxygenase-2 mRNA were also time dependently increased (P < 0.01, each). Furthermore, administration of rIL-1beta (10 microg/kg, i.p.) significantly induced the expressions of IL-1beta and IL-6 mRNA in colonic mucosa from non-treated mice (P < 0.01). Anti-mIL-1beta antibody treatments (50 microg/kg, i.p.) attenuated DSS-induced body weight reduction and shortening of the colorectum (P < 0.05, each), and abrogated the expressions of IL-1beta and IL-6 mRNA in colonic mucosa (P < 0.01, each). Our results evidently support the previous findings that IL-1beta is involved in the development of DSS-induced experimental colitis in mice, and strongly suggest that IL-1beta targets itself and IL-6 for progressing colonic inflammation.
authors.affiliation: Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Japan.
authors.forename: Ki Han
authors.initials: KH
authors.lastname: Kwon
authors.forename: Akira
authors.initials: A
authors.lastname: Murakami
authors.forename: Ryohei
authors.initials: R
authors.lastname: Hayashi
authors.forename: Hajime
authors.initials: H
authors.lastname: Ohigashi
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced* / Q000473:pathology; D016264:Dextran Sulfate; D015870:Gene Expression / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000473:pathology*; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000378:metabolism; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D016264:Dextran Sulfate