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The effects of TGF-β1 on the expression of type IV collagenases in mouse peritoneal macrophages

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Abstract

Transforming growth factor-β (TGF-β) is a pleiotropic cytokine that plays a critical role in modulating immune response and inflammation. We have investigated the effects of TGF-β1 on the expression of type IV collagenases, matrix metalloproteinase (MMP)-2 and MMP-9, in mouse peritoneal macrophages. TGF-β1 alone enhanced the secretion of MMP-9, while it blocked lipopolysaccharide (LPS)-stimulated MMP-9 production. We have shown that this biphasic effect of TGF-β1 is exerted at the mRNA level of the MMP-9 gene. Although TGF-β1 increased both basal and LPS-induced MMP-2 production at the protein and mRNA levels, the extent of the increase was smaller in LPS-activated macrophages than in control macrophages. The expression of type I and type II receptors for TGF-β was significantly decreased upon activation, suggesting that the lesser effect of TGF-β1 in activated macrophages may result from the decreased expression of TGF-β receptors. In addition, the expression of endogenous TGF-β1 mRNA was decreased significantly in activated macrophages. These findings suggest that activated macrophages not only produce less TGF-β1, but also respond less well to TGF-β to provide for inflammatory response.

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Acknowledgments

We would like to thank the National Hormone and Pituitary Program for providing human recombinant follistatin. This work was supported by a Grant-in-Aid for Scientific Research (18580300) from the Japan Society for the Promotion of Science (to K.O.) and a grant for the Chemical Biology Research Program from RIKEN.

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Authors and Affiliations

  1. Laboratory of Cellular Biochemistry, RIKEN, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan

    Kenji Ogawa & Masafumi Tsujimoto

  2. Division of Applied Biosciences, Kyoto University Graduate School of Agriculture, Kitashirakawa Oiwakecho, Kyoto, 606-8502, Japan

    Masayuki Funaba

  3. Molecular Ligand Discovery Research Team, Chemical Genomics Research Group, ASI, RIKEN, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan

    Kenji Ogawa

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  1. Kenji Ogawa
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  2. Masayuki Funaba
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  3. Masafumi Tsujimoto
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Correspondence to Kenji Ogawa.

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Ogawa, K., Funaba, M. & Tsujimoto, M. The effects of TGF-β1 on the expression of type IV collagenases in mouse peritoneal macrophages. Mol Biol Rep 38, 1451–1456 (2011). https://doi.org/10.1007/s11033-010-0250-8

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  • DOI: https://doi.org/10.1007/s11033-010-0250-8

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