Interleukin-13 Enhances Cyclooxygenase-2 Expression in Activated Rat Brain Microglia: Implications for Death of Activated Microglia.
From: Department of Pharmacology, Ajou University School of Medicine, Suwon 442-721, Korea.
Journal of immunology (Baltimore, Md. : 1950)
- Publish Date: Jul 2006
- ISSN: 0022-1767
- Volume: 177
- Issue: 2
- Pages: 1323-9
- Medium: Print
- Language: English
- Citation (JAMA): Yang Myung-Soon, Ji Kyung-Ae, Jeon Sae-Bom, et al. Interleukin-13 Enhances Cyclooxygenase-2 Expression in Activated Rat Brain Microglia: Implications for Death of Activated Microglia.. J. Immunol. Jul 2006;177:1323-9
Abstract
Brain inflammation has recently attracted widespread interest because it is a risk factor for the onset and progression of brain diseases. In this study, we report that cyclooxygenase-2 (COX-2) plays a key role in the resolution of brain inflammation by inducing the death of microglia. We previously reported that IL-13, an anti-inflammatory cytokine, induced the death of activated microglia. These results revealed that IL-13 significantly enhanced COX-2 expression and production of PGE(2) and 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)) in LPS-treated microglia. Two other anti-inflammatory cytokines, IL-10 and TGF-beta, neither induced microglial death nor enhanced COX-2 expression or PGE(2) or 15d-PGJ(2) production. Therefore, we hypothesized that the effect of IL-13 on COX-2 expression may be linked to death of activated microglia. We found that COX-2 inhibitors (celecoxib and NS398) suppressed the death of microglia induced by a combination of LPS and IL-13 and that exogenous addition of PGE(2) and 15d-PGJ(2) induced microglial death. Agonists of EP2 (butaprost) and peroxisome proliferator-activated receptor gamma (ciglitazone) mimicked the effect of PGE(2) and 15d-PGJ(2), and an EP2 antagonist (AH6809) and a peroxisome proliferator-activated receptor gamma antagonist (GW9662) suppressed microglial death induced by LPS in combination with IL-13. In addition, IL-13 potentiated LPS-induced activation of JNK, and the JNK inhibitor SP600125 suppressed the enhancement of COX-2 expression and attenuated microglial death. Taken together, these results suggest that IL-13 enhanced COX-2 expression in LPS-treated microglia through the enhancement of JNK activation. Furthermore, COX-2 products, PGE(2) and 15d-PGJ(2), caused microglial death, which terminates brain inflammation.
Mesh Headings (Keywords): Animals, Brain, Cell Death, Cells, Cultured, Cyclooxygenase 2, Interleukin-10, Interleukin-13, Interleukin-4, JNK Mitogen-Activated Protein Kinases, Lipopolysaccharides, Microglia, PPAR gamma, Rats, Rats, Sprague-Dawley, Receptors, Prostaglandin E, Transforming Growth Factor beta, Up-Regulation
Check for Full Text / PubMed Unique Identifier (PMID): 16818793
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