Interleukin-10 and Th2 cytokines differentially regulate osteopontin expression in human monocytes and dendritic cells.
Osteopontin (OPN) is a pleiotrophic phosphoprotein involved in homeostatic and pathophysiologic responses. It is known to be a chemotactic cytokine for dendritic cells (DCs), a critical cell type in both innate and adaptive immune responses. We report herein a contrasting role of interleukin-10 (IL-10) and Th2 cytokines in the regulation of OPN expression in human monocytes and monocyte-derived DCs (Mo-DCs). Our results showed first that the expression of OPN in monocytes and Mo-DCs was induced in a time-dependent and dose-dependent manner by IL-10 but was inhibited by IL-4 or IL-13. Further, the basal level of OPN expression was also inhibited by IL-4. This inhibitory effect of IL-4 was associated with a faster decay of OPN transcripts and a decreased proximal promoter activity of OPN in IL-4-treated cells. These results demonstrate a novel role of IL-10 and Th2 cytokines in the regulation of DC function through their contrasting regulatory activities on the expression of OPN.
Konno
Satoshi
S
Johns Hopkins Asthma and Allergy Center, Baltimore, MD 21224, USA.
Eckman
John A
JA
Plunkett
Beverly
B
Li
Xinfang
X
Berman
Jeffery S
JS
Schroeder
John
J
Huang
Shau-Ku
SK
D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D005786:Gene Expression Regulation; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology*; D018793:Interleukin-13 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D053495:Osteopontin; D020871:RNA Stability / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D012795:Sialoglycoproteins / Q000235:genetics* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology
D018793:Interleukin-13; D007378:Interleukins; D012333:RNA, Messenger; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D053495:Osteopontin; D016753:Interleukin-10; D015847:Interleukin-4