title: Regulation of Toll-like receptor 4 expression in mouse colon by macrophage migration inhibitory factor.
abstract: Recent studies have indicated that macrophage migration inhibitory factor (MIF) and Toll-like receptor (TLR) play an important role in the regulation of innate immune responses. In this study, we investigated the effect of MIF on the expression of TLR4, a receptor that recognizes lipopolysaccharide, in colon using MIF-deficient mice. TLR4 mRNA expression in the colon tissues was determined by northern blot analysis. Western blot analysis and immunohistochemistry in the colon tissues were performed to evaluate the expression of TLR4 protein. The expressions of TLR4 mRNA and protein were remarkably down-regulated in colon tissues of MIF-deficient mice compared with wild-type mice and up-regulated by treatment with recombinant MIF. Immunohistochemical study revealed the presence of TLR4-positive staining in mononuclear cells in the lamina propria and intraepithelial mononuclear cells as well as weak staining in epithelial cells and crypts in colon tissues of wild-type mice. In contrast, MIF-deficient mice did not show TLR4-positive staining in the colonic mucosa. In MIF-deficient mice injected with recombinant mouse MIF (rMIF), TLR4-positive staining cells were observed in colon tissues similar to the findings in wild-type mice. Administration of dextran sulfate sodium (DSS) up-regulated the expression of TLR4 in the colons of WT mice but not in those of MIF-deficient mice. Furthermore, pretreatment with rMIF up-regulated the expression of TLR4 in response to DSS in MIF-deficient mice. Our results suggest that MIF affects the expression of TLR4 in mouse colon under both normal and colitic conditions.
authors.affiliation: Department of Gastroenterology and Hematology, Hokkaido University Graduate School of Medicine, Kita-15, Nishi-7, Kita-ku, 060-8638, Sapporo, Japan. tokawara@med.hokudai.ac.jp
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ohkawara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takeda
authors.forename: Kencho
authors.initials: K
authors.lastname: Miyashita
authors.forename: Morie
authors.initials: M
authors.lastname: Nishiwaki
authors.forename: Toshinori
authors.initials: T
authors.lastname: Nakayama
authors.forename: Masaru
authors.initials: M
authors.lastname: Taniguchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Yoshiki
authors.forename: Junji
authors.initials: J
authors.lastname: Tanaka
authors.forename: Junji
authors.initials: J
authors.lastname: Takana
authors.forename: Masahiro
authors.initials: M
authors.lastname: Imamura
authors.forename: Toshiro
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Masahiro
authors.initials: M
authors.lastname: Asaka
authors.forename: Jun
authors.initials: J
authors.lastname: Nishihira
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003106:Colon / Q000187:drug effects* / Q000378:metabolism*; D016264:Dextran Sulfate / Q000494:pharmacology; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D008263:Macrophage Migration-Inhibitory Factors / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013047:Specific Pathogen-Free Organisms; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis*
chemical_list: D008263:Macrophage Migration-Inhibitory Factors; D012333:RNA, Messenger; D011994:Recombinant Proteins; D051197:Toll-Like Receptor 4; D016264:Dextran Sulfate