Microglial production of TNF-alpha is induced by activated T lymphocytes. Involvement of VLA-4 and inhibition by interferonbeta-1b.
basic_science · Level V
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- Record sourced from PubMed, PMID 9239408.
- Also identified by PMC identifier 508228.
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Abstract
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.
Medical subject headings
- Integrins
- Microglia
- Receptors, Lymphocyte Homing
- T-Lymphocytes
- Tumor Necrosis Factor-alpha