TGF-beta regulation of human macrophage scavenger receptor CD163 is Smad3-dependent.
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-beta (TGF-beta) markedly reduces expression of CD163. Treatment of primary human monocytes with TGF-beta 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-beta 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-beta, and suppression was dependent on Smad3 expression. These results define a novel function for TGF-beta and implicate an important role for CD163 in the host response to inflammation.
Pioli
Patricia A
PA
Department of Physiology, Dartmouth Medical School, Lebanon, NH 03756, USA. pioli@dartmouth.edu
Goonan
Katie E
KE
Wardwell
Kathleen
K
Guyre
Paul M
PM
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D015703:Antigens, CD / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D003600:Cytosol; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D015536:Down-Regulation; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D051900:Smad3 Protein; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D000098902:CD163 Antigen
D000893:Anti-Inflammatory Agents; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C497790:SMAD3 protein, human; D051900:Smad3 Protein; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D003907:Dexamethasone