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Interleukin-13 enhances cyclooxygenase-2 expression in activated rat brain microglia: implications for death of activated microglia.

Yang, MS; Ji, KA; Jeon, SB; Jin, BK; Kim, SU; Jou, I; Joe, E
Journal of immunology (Baltimore, Md. : 1950), 177(2):1323-1329, 2006
Journal Title
Journal of immunology (Baltimore, Md. : 1950)
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 terms
AnimalsBrain/cytologyBrain/enzymology*Brain/immunology*Cell Death/immunologyCells, CulturedCyclooxygenase 2/biosynthesis*Cyclooxygenase 2/physiologyInterleukin-10/physiologyInterleukin-13/physiology*Interleukin-4/physiologyJNK Mitogen-Activated Protein Kinases/physiologyLipopolysaccharides/pharmacologyMicroglia/cytologyMicroglia/enzymology*Microglia/immunology*PPAR gamma/physiologyRatsRats, Sprague-DawleyReceptors, Prostaglandin E/physiologyReceptors, Prostaglandin E, EP2 SubtypeTransforming Growth Factor beta/physiologyUp-Regulation/immunology*
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
Journal Papers > Research Organization > Institute for Medical Sciences
Journal Papers > School of Medicine / Graduate School of Medicine > Neurology
AJOU Authors
양, 명순진, 병관김, 승업주, 일로조, 은혜
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