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TGF‐β regulation of human macrophage scavenger receptor CD163 is Smad3‐dependent
Author(s) -
Pioli Patricia A.,
Goonan Katie E.,
Wardwell Kathleen,
Guyre Paul M.
Publication year - 2004
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1203617
Subject(s) - cd163 , biology , transforming growth factor , microbiology and biotechnology , inflammation , scavenger receptor , macrophage , receptor , downregulation and upregulation , cytokine , transforming growth factor beta , immunology , endocrinology , gene , biochemistry , lipoprotein , cholesterol , in vitro
Tight regulation of the inflammatory response is essential for the maintenance of physiologic homeostasis. A potentially important mediator of this process is CD163, a macrophage‐specific member of the scavenger receptor cysteine‐rich family. CD163 surface expression is up‐regulated by glucocorticoids and the anti‐inflammatory cytokine interleukin‐10, and CD163 is shed acutely from the cell surface in response to lipopolysaccharide. We now demonstrate that transforming growth factor‐β (TGF‐β) markedly reduces expression of CD163. Treatment of primary human monocytes with TGF‐β inhibited basal as well as dexamethasone‐induced CD163 mRNA and protein expression. De novo protein synthesis was not required for this inhibition, suggesting that TGF‐β regulates CD163 expression transcriptionally. To delineate this transcriptional regulation, a 2.5‐kb fragment of the CD163 promoter was isolated. This promoter was inhibited by TGF‐β, and suppression was dependent on Smad3 expression. These results define a novel function for TGF‐β and implicate an important role for CD163 in the host response to inflammation.