[Current topics in the regulation of prostanoids--4. The feedback regulation by PPAR-gamma].
Department of Anesthesiology, Yokohama City University, School of Medicine.Masui. The Japanese journal of anesthesiology 03/1999; 48(2):146-51.
Recently, it has become known that lipophilic hormones such as steroids and thyroid hormones, or fat-soluble vitamins (vitamins A and D) pass through the cellular membrane and bind to the nuclear receptor superfamily to act as transcription factors. The metabolite of prostaglandin (PG) D2, 15-deoxy-D12,14PGJ2, has been identified as the ligand for peroxisome proliferator-activated receptor gamma (PPAR-gamma), a member of the nuclear receptor superfamily. It forms a transcription factor and is responsible not only for the differentiation of fibroblasts to adipocytes, but also for the regulation of activated macrophages. It is now known that thiazolidinediones and non-steroidal anti-inflammatory drugs classified as cyclooxygenase blockers such as indomethacine and ibuprofen also act as PPAR-gamma agonists and inhibit cytokine production from activated macrophages. PPAR-gamma has become recognized as a new therapeutic target for inflammation control.
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ABSTRACT: The inflammatory response accompanies and exacerbates the developing injury after cerebral ischemia. Ibuprofen, a non-steroidal anti-inflammatory drug, has been shown to attenuate injuries in animal models of various neurological diseases. In the present study, we investigated ibuprofen's neuroprotective effects in rats exposed to transient forebrain ischemia and in cultures exposed to oxygen glucose deprivation (OGD). Rats treated with ibuprofen after transient forebrain ischemia displayed long-lasting protection of CA1 hippocampal neurons. There were selective increases in interleukin-1 receptor antagonist gene and protein expression in ibuprofen-treated OGD microglia. Furthermore, treatment with ibuprofen in neuron/microglia co-cultures increased the number of surviving HC2S2 neurons against OGD whereas IL-1ra neutralizing antibody reversed the ibuprofen-induced neuroprotection. The data indicate that ibuprofen-induced IL-1ra secretion is involved in neuroprotection against ischemic conditions.
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