Microglial production of TNF-alpha is induced by activated T lymphocytes. Involvement of VLA-4 and inhibition by interferonbeta-1b.
TNF-alpha is a proinflammatory cytokine involved in many inflammatory conditions such as Crohn's disease, rheumatoid arthritis, cachexia, AIDS, and multiple sclerosis (MS). TNF-alpha is produced mainly by cells of the macrophage lineage, which includes microglia in the central nervous system. Here, we describe a mechanism through which TNF-alpha is generated by microglia. We show that activated human T lymphocytes induce the microglial production of TNF-alpha, and that is attenuated by a functional blocking antibody to CD49d, the alpha chain of the VLA-4 integrin on T cells. We also report that interferonbeta-1b (IFNbeta-1b), a drug that alleviates symptoms in MS, downregulates the expression of CD49d and reduces TNF-alpha production, mechanisms which can help account for its efficacy in MS.
Chabot
S
S
Neuroimmunology Unit, Department of Neurology and Neurosurgery, McGill University, Montreal Neurological Institute, Montreal, Quebec, Canada H3A 2B4.
Williams
G
G
Yong
V W
VW
D002478:Cells, Cultured; D018920:Coculture Techniques; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000276:immunology*; D016899:Interferon-beta / Q000494:pharmacology; D008213:Lymphocyte Activation; D017628:Microglia / Q000276:immunology* / Q000473:pathology; D016201:Receptors, Lymphocyte Homing / Q000276:immunology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D039041:Integrin alpha4beta1; D016023:Integrins; D016201:Receptors, Lymphocyte Homing; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016899:Interferon-beta