Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/40297
標題: IL-13 downregulates PPAR-gamma/heme oxygenase-1 via ER stress-stimulated calpain activation: aggravation of activated microglia death
作者: Liu, S.H.
許美鈴
Yang, C.N.
Pan, H.C.
Sung, Y.J.
Liao, K.K.
Chen, W.B.
Lin, W.Z.
Sheu, M.L.
關鍵字: Microglia;Interleukin-13;Calpain;PPAR-gamma;Heme oxygenase-1;endoplasmic-reticulum stress;heme oxygenase-1;oxidative stress;cell-death;neurodegenerative disorders;cyclooxygenase-2 expression;parkinsons-disease;alzheimers-disease;brain-injury;mouse model
Project: Cellular and Molecular Life Sciences
期刊/報告no:: Cellular and Molecular Life Sciences, Volume 67, Issue 9, Page(s) 1465-1476.
摘要: 
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.
URI: http://hdl.handle.net/11455/40297
ISSN: 1420-682X
DOI: 10.1007/s00018-009-0255-4
Appears in Collections:生物醫學研究所

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