Histochemistry and Cell Biology

, Volume 125, Issue 5, pp 575–582

Regulation of Toll-like receptor 4 expression in mouse colon by macrophage migration inhibitory factor

  • Tatsuya Ohkawara
  • Hiroshi Takeda
  • Kencho Miyashita
  • Morie Nishiwaki
  • Toshinori Nakayama
  • Masaru Taniguchi
  • Takashi Yoshiki
  • Junji Takana
  • Masahiro Imamura
  • Toshiro Sugiyama
  • Masahiro Asaka
  • Jun Nishihira
Original paper

DOI: 10.1007/s00418-005-0092-y

Cite this article as:
Ohkawara, T., Takeda, H., Miyashita, K. et al. Histochem Cell Biol (2006) 125: 575. doi:10.1007/s00418-005-0092-y

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.

Keywords

Colon Dextran sulfate sodium Macrophage migration inhibitory factor Toll-like receptor 4 Immunohistochemistry 

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Tatsuya Ohkawara
    • 1
  • Hiroshi Takeda
    • 1
  • Kencho Miyashita
    • 1
  • Morie Nishiwaki
    • 2
  • Toshinori Nakayama
    • 3
  • Masaru Taniguchi
    • 4
  • Takashi Yoshiki
    • 2
  • Junji Takana
    • 5
  • Masahiro Imamura
    • 5
  • Toshiro Sugiyama
    • 6
  • Masahiro Asaka
    • 1
  • Jun Nishihira
    • 2
  1. 1.Department of Gastroenterology and HematologyHokkaido University Graduate School of MedicineSapporoJapan
  2. 2.Department of Research and DevelopmentGeneticLabSapporoJapan
  3. 3.Department of Molecular Immunology, Graduate School of MedicineChiba UniversityChibaJapan
  4. 4.Department of Medical Immunology, Graduate School of MedicineChiba UniversityChibaJapan
  5. 5.Department of Hematology and OncologyHokkaido University Graduate School of MedicineSapporoJapan
  6. 6.Third Department of Internal MedicineToyama Medical and Pharmaceutical UniversityToyamaJapan

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