G-protein-coupled receptor independent, immunomodulatory properties of chemokine CXCL9 |
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Authors: | Jiang-Hong Gong Erin F. Nicholls Melissa R. Elliott Karsten Hokamp Fiona M. Roche Charles Y.K. Cheung Reza Falsafi D.M.E. Bowdish |
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Affiliation: | a Centre for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z4 b Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada V5A 1S6 c Department of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada |
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Abstract: | Certain chemokines possess anti-angiogenic and antibacterial activity, in addition to their ability to recruit leukocytes. Herein, we demonstrate that CXCL9/MIG induces the expression, by a monocytic cell line and peripheral blood mononuclear cells, of a variety of chemokines including CXCL8/IL-8, CCL3/MIP-1α, CCL4/MIP-1β, CCL2/MCP-1 in a pertussis toxin insensitive manner. Similarly, another cationic chemokine CCL20/MIP-3α, but not the non-cationic chemokines CCL2 or CCL3, stimulated monocytic cells to produce substantial amounts of CXCL8 and CCL3. Microarray experiments demonstrated that CXCL9, but not CCL2, induced the expression of hundreds of genes, many of which have known or proposed immunomodulatory functions. Induction of CXCL8 required the p38 and ERK1/2 mitogen-activated protein kinases but not NFκB, JAK-STAT or JNK signaling pathways. These results collectively demonstrate that CXCL9 has immunomodulatory functions that are not mediated through a G-protein coupled receptor and may possess additional roles in host defenses against infection. |
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Keywords: | GPCR, G-protein coupled receptor GM-CSF, granulocyte-macrophage colony stimulating factor MIG/CXCL9, monokine induced by interferon gamma IL-8/CXCL8, interleukin-8 IP-10/CXCL10, interferon gamma inducible protein 10 MIP-1α/CCL3, macrophage inflammatory protein 1 α MCP-1/CCL2, monocyte chemoattractant protein 1 MIP-3α/LARC/CCL20, macrophage inflammatory protein-3 α MIP-1β/CCL4, macrophage inflammatory protein 1 β PBMC, peripheral blood mononuclear cells P.T., pertussis toxin |
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