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IL-13 downregulates PPAR-gamma/heme oxygenase-1 via ER stress-stimulated calpain activation: aggravation of activated microglia death.

Authors :
Liu SH
Yang CN
Pan HC
Sung YJ
Liao KK
Chen WB
Lin WZ
Sheu ML
Source :
Cellular and molecular life sciences : CMLS [Cell Mol Life Sci] 2010 May; Vol. 67 (9), pp. 1465-76. Date of Electronic Publication: 2010 Mar 10.
Publication Year :
2010

Abstract

Interleukin 13 (IL-13) has been shown to induce the death of activated microglia. We observed that IL-13, but not IL-4 or IL-10, significantly enhanced endoplasmic reticulum (ER) stress induction, apoptosis and death in microglia activated by lipopolysaccharide (LPS). IL-13 enhanced ER stress-regulated calpain activation and calpain-II expression in LPS-activated microglia. Calpain-II siRNA effectively reversed the IL-13 + LPS-activated caspase-12 activation. Expression of heme oxygenase-1 (HO-1) and peroxisome proliferator-activated receptor-gamma (PPAR-gamma) was also increased in activated microglia, and this was effectively blocked by IL-13 and recombinant calpain. Both HO-1 inhibitor and PPAR-gamma antagonist augmented, but calpain inhibitor and PPAR-gamma agonists reversed, apoptosis induction in activated microglia. Transfection of PPAR-gamma siRNA effectively inhibited HO-1 protein expression in activated microglia. LPS stimulated transcriptional activation of HO-1 via an increase in PPAR-gamma DNA binding activity, which was reversed by IL-13. These results indicate that an ER stress-related calpain-down-regulated PPAR-gamma/HO-1 pathway is involved in the IL-13-enhanced activated death of microglia.

Details

Language :
English
ISSN :
1420-9071
Volume :
67
Issue :
9
Database :
MEDLINE
Journal :
Cellular and molecular life sciences : CMLS
Publication Type :
Academic Journal
Accession number :
20221786
Full Text :
https://doi.org/10.1007/s00018-009-0255-4