HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yang, M.-S. Articles by Joe, E. Search for Related Content PubMed PubMed Citation Articles by Yang, M.-S. Articles by Joe, E.

Interleukin-13 Enhances Cyclooxygenase-2 Expression in Activated Rat Brain Microglia: Implications for Death of Activated Microglia¹

Myung-Soon Yang^*,, Kyung-Ae Ji^*,, Sae-Bom Jeon, Byung-Kwan Jin^,, Seung U. Kim^,,¶, Ilo Jou^*, and Eunhye Joe^2,*,,

^* Department of Pharmacology, Ajou University School of Medicine, Suwon, Korea; Neuroscience Graduate Program, Ajou University School of Medicine, Suwon, Korea; Brain Disease Research Center, Ajou University School of Medicine, Suwon, Korea; Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon, Korea; and ^¶ Department of Neurology, University of British Columbia, Vancouver, Canada

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 PGE₂ and 15-deoxy-^12,14-PGJ₂ (15d-PGJ₂) in LPS-treated microglia. Two other anti-inflammatory cytokines, IL-10 and TGF-, neither induced microglial death nor enhanced COX-2 expression or PGE₂ or 15d-PGJ₂ 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 PGE₂ and 15d-PGJ₂ induced microglial death. Agonists of EP2 (butaprost) and peroxisome proliferator-activated receptor (ciglitazone) mimicked the effect of PGE₂ and 15d-PGJ₂, and an EP2 antagonist (AH6809) and a peroxisome proliferator-activated receptor 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, PGE₂ and 15d-PGJ₂, caused microglial death, which terminates brain inflammation.

This article has been cited by other articles:

				J. A. Schwartzbaum, A. Ahlbom, S. Lonn, B. Malmer, A. Wigertz, A. Auvinen, A. J. Brookes, H. Collatz Christensen, R. Henriksson, C. Johansen, et al. An International Case-Control Study of Interleukin-4R{alpha}, Interleukin-13, and Cyclooxygenase-2 Polymorphisms and Glioblastoma Risk Cancer Epidemiol. Biomarkers Prev., November 1, 2007; 16(11): 2448 - 2454. [Abstract] [Full Text] [PDF]