Glucocorticoid suppression of CX3CL1 (fractalkine) by reduced gene promoter recruitment of NF-κB

Pankaj K. Bhavsar, Maria B. Sukkar, Nadia Khorasani, Kang Yun Lee, Kian Fan Chung

研究成果: 雜誌貢獻文章同行評審

44 引文 斯高帕斯(Scopus)


Glucocorticoids are an important anti-inflammatory treatment of many inflammatory diseases including asthma. However, the mechanisms by which they mediate their suppressive effects are not fully understood. Respiratory epithelial cells are a source of CX3CL1 (fractalkine), which mediates cell adhesion and acts as a chemoattractant for monocytes, T cells, and mast cells. We show, in lung A549 epithelial cells, that the tumor necrosis factor-α (TNF-α) and IFNγ synergistically induced protein release and mRNA expression of CX3CL1 is inhibited by dexamethasone, without interfering with cytokine-induced nuclear translocation of NF-κB, and by an inhibitor of IκB kinase 2, AS602868. DNA binding assays confirmed the ability of NF-κB to bind to the proximal CX3CL1 promoter. Chromatin immunoprecipitation assays showed a 5-fold increase in the recruitment of NF-κB to the CX3CL1 gene promoter in response to IFNγ/TNF-α; this too was reversed by dexamethasone. In contrast, dexamethasone did not displace NF-κB from the granulocyte-macrophage colony-stimulating factor gene promoter. We conclude that CX3CL1 expression is regulated through the NF-κB pathway and that dexamethasone inhibits CX3CL1 expression through a glucocorticoid receptor-dependent (RU486 sensitive) mechanism. This study also provides support for the action of glucocorticoids mediating their suppressive effects on expression by interfering with the binding of transcriptional activators at native gene promoters.

頁(從 - 到)1807-1816
期刊FASEB Journal
出版狀態已發佈 - 六月 2008

ASJC Scopus subject areas

  • 農業與生物科學(雜項)
  • 生物化學、遺傳與分子生物學 (全部)
  • 生物化學
  • 細胞生物學
  • 醫藥 (全部)


深入研究「Glucocorticoid suppression of CX3CL1 (fractalkine) by reduced gene promoter recruitment of NF-κB」主題。共同形成了獨特的指紋。