Cytokine Induction of MIP-1α and MIP-1β in Human Fetal Microglia

作者：Carrie M. McManus, Celia F. Brosnan, Joan W. Berman · 发表于：The Journal of Immunology · 年份：1998 · 被引用次数：150 · 研究领域：Neuroinflammation and Neurodegeneration Mechanisms、HIV Research and Treatment、interferon and immune responses

Abstract Leukocyte infiltration into the central nervous system (CNS) is a key event in the inflammatory processes of neuroimmunologic diseases. Microglia, resident macrophages of the CNS, may contribute to this process by elaborating chemoattractants that are capable of recruiting leukocytes across the blood-brain barrier. Such factors have been detected in the CNS of animal models of multiple sclerosis and in the brains of human and nonhuman primates with AIDS encephalitis. As the expression of these chemoattractants may play an important role in the initiation and progression of neuroimmunologic diseases, we analyzed expression of the chemokines MIP-1α, MIP-1β, MCP-1, and RANTES in human fetal microglial cultures. Unstimulated microglia expressed minimal levels of MIP-1α, MIP-1β, and MCP-1, while RANTES was undetectable. In response to LPS, TNF-α, or IL-1β, both MIP-1α and MIP-1β were induced at the mRNA and protein levels in a dose- and time-dependent manner. IFN-γ did not significantly induce chemokine expression. MCP-1 was detectable in LPS- and cytokine-treated microglia. TGF-β, a cytokine with down-modulatory effects on other cell types, had little effect on chemokine expression in microglia when used concomitantly before or during treatment with LPS. These results illustrate the ability of certain inflammatory stimuli to induce expression of MIP-1α, MIP-1β, and MCP-1 by human fetal microglia. The expression of these chemoattractants may function to recruit inflammato...