Recombinant human interleukin 1 beta induces production of prostaglandins in primary human fetal astrocytes and immortalized human fetal astrocyte cultures.
Astrocytes play an important role in initiating and modulating inflammatory responses within the central nervous system. Extensive studies in rodents have shown that TPA, substance P, calcium ionophore A21387, and lipopolysaccharide (LPS) induce formation and release of arachidonic acid metabolites which have immunoregulatory properties. To better understand the immunopathology of brain injury, we studied the role of inflammatory cytokines such as tumor necrosis factor alpha, interleukin (IL) 6, IL-2, interferon gamma and IL-1 beta in the production of arachidonic acid metabolites in cells from fetal human brain. Among these cytokines, only IL-1 beta significantly stimulated production of prostaglandins E2 and F2 alpha but not PGD2, thromboxane B2 and 6-keto-PGF1 alpha. Under our experimental conditions, these astrocyte cultures did not produce metabolites in the lipoxygenase pathway such as leukotrienes B4 and C4 upon IL-1 beta stimulation. The stimulatory effects of IL-1 beta on the induction of arachidonic acid metabolites have been studied in various human cell types but not in astrocytes. Human astrocyte production of PGF2 alpha and PGE2 but not PGD2, 6-keto-PGF1 alpha and TXB2 when stimulated by IL-1 beta, is thus a novel finding. This observation should initiate investigations into the mechanism of arachidonic acid metabolism and the role of its metabolites in inflammation in the human nervous system.
Dayton
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Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892-4164, USA.
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D016718:Arachidonic Acid / Q000502:physiology; D001253:Astrocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D010741:Phospholipases A / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis*; D011493:Protein Kinase C / Q000502:physiology; D011994:Recombinant Proteins
D016207:Cytokines; D007375:Interleukin-1; D008070:Lipopolysaccharides; D011453:Prostaglandins; D011994:Recombinant Proteins; D016718:Arachidonic Acid; D011493:Protein Kinase C; D010741:Phospholipases A