Cytokine regulation of CC and CXC chemokine expression by human astrocytes.
Chemokines constitute a large family of secreted proteins that function as chemoattractants and activators of leukocytes. Astrocytes, the major glial cell type in the central nervous system (CNS), are a source of chemokine production within diseased brain. As such, we have examined the production of chemokines by human astroglioma cell lines and primary human astrocytes treated with a variety of stimuli, including LPS, TNF-alpha, IFN-gamma and IL-1beta. In addition, IL-6 in conjunction with the soluble IL-6 receptor (sIL-6R), and hybrid IL-6 (H-IL-6), a highly active fusion protein of sIL-6R and IL-6, were tested for their ability to induce chemokine expression. The findings presented herein demonstrate that both human astroglioma cell lines and primary human astrocytes express the CXC chemokines IP-10 and IL-8 and the CC chemokines MCP-1 and RANTES in response to TNF-alpha and IL-1beta. IFN-gamma induced the expression of IP-10, but not of IL-8, MCP-1 or RANTES. Surprisingly, IL-6/sIL-6R and H-IL-6 had little or no effect on chemokine expression in these cells. The effect of TGF-beta on chemokine expression in human astroglioma cell lines and astrocytes was also examined. TGF-beta alone had little or no effect on RANTES, MCP-1 and IL-8 expression; however, TGF-beta synergized with TNF-alpha to enhance MCP-1 expression in both astroglioma cells and primary astrocytes. An inhibitory effect of TGF-beta on TNF-alpha and IL-1beta induced RANTES and IL-8 expression was observed in human astroglioma cells. In contrast, TGF-beta enhanced TNF-alpha and IL-1beta induction ofIL-8 production by human astrocytes. These findings document a complex pattern of chemokine regulation by the pleiotropic cytokine TGF-beta with both enhancing and inhibitory effects.
Oh
J W
JW
Department of Cell Biology, University of Alabama at Birmingham, USA.
Schwiebert
L M
LM
Benveniste
E N
EN
D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000378:metabolism; D018946:Chemokine CCL5 / Q000378:metabolism; D054357:Chemokine CXCL10; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D019743:Chemokines, CXC / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018932:Chemokine CCL2; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D018925:Chemokines; D019743:Chemokines, CXC; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D019947:Receptors, Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma