27 324

Cited 47 times in

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

Authors
Yang, MS; Ji, KA; Jeon, SB; Jin, BK; Kim, SU; Jou, I; Joe, E
Citation
Journal of immunology (Baltimore, Md. : 1950), 177(2):1323-1329, 2006
Journal Title
Journal of immunology (Baltimore, Md. : 1950)
ISSN
0022-17671550-6606
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 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*
PMID
16818793
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
양명순진병관김승업주일로조은혜
Full Text Link
Export
RIS (EndNote)
XLS (Excel)
XML

qrcode

해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse