TGF-β regulation of human macrophage scavenger receptor CD163 is Smad3-dependent

Journal of Leukocyte Biology

Paul M. Guyre¹  Patricia A. Pioli¹  Katie E. Goonan¹  Kathleen Wardwell¹ 

[1] Department of Physiology, Dartmouth Medical School, Lebanon, New HampshireDepartment of Physiology, Dartmouth Medical School, Lebanon, New HampshireDepartment of Physiology, Dartmouth Medical School, Lebanon, New Hampshire

关键词: cytokine;    inflammation;    glucocorticoid;    signal transduction;   

DOI  :  10.1189/jlb.1203617

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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.

【 授权许可】

Unknown