Macrophage-colony stimulating factor and interleukin-34 induce chemokines in human whole blood |
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| Institution: | 1. College of Animal Science, South China Agricultural University, Guangzhou 510642, Guangdong Province, PR China;2. State Key Laboratory of Biocontrol/ Key Laboratory of Aquatic Product Safety (Sun Yat-Sen University), Ministry of Education, The School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, Guangdong Province, PR China;3. School of Bioscience and Biotechnology, South China University of Technology, Guangzhou 510006, PR China;1. Department of Molecular and Pharmacological Neuroscience, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan;2. Department of Dermatology, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan;1. Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University, Fort Lauderdale, FL, 33314, United States;2. Institute for Neuro Immune Medicine, Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL, 33143, United States |
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| Abstract: | The aim of this study is to investigate if macrophage-colony stimulating factor (M-CSF) or interleukin-34 (IL-34) induces cytokines or chemokines using human whole blood (HWB) and if an M-CSF- or IL-34-induced cytokine or chemokine production from HWB is inhibited by soluble M-CSF receptor or c-FMS kinase inhibitors. Among eight cytokines or growth factors tested, only IL-6 level was increased by up to 6-fold by M-CSF or IL-34 in HWB. In contrast, chemokine levels (IP-10/CXCL10, IL-8/CXCL8, and MCP-1/CCL2) were dramatically increased by M-CSF or IL-34 in HWB while exhibiting a large variation among donors. Variability of the MCP-1 signal induced by M-CSF or IL-34 was relatively less among donors compared to the IP-10 and IL-8 signals. The elevation of these chemokine levels was significantly decreased by soluble M-CSF receptor, indicating the elevation of these chemokines was mediated by M-CSF or IL-34. Furthermore, GW2580, a c-FMS kinase inhibitor, inhibited the induction of MCP-1 by M-CSF or IL-34 in a concentration dependent manner. These indicate MCP-1 is the most appropriate chemokine target for a chemokine release assay to evaluate the potency of c-FMS kinase inhibitors and MCP-1 release assay using HWB would be useful, relevant tool for translational pharmacology of c-FMS kinase inhibitors. |
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