IL-13 downregulates PPAR-γ/heme oxygenase-1 via ER stress-stimulated calpain activation: aggravation of activated microglia death
| Autor: | Wen Zheng Lin, Shing-Hwa Liu, Meei-Ling Sheu, Ko Kaung Liao, Wen Bao Chen, Hung Chuan Pan, Cheng Ning Yang, Yen-Jen Sung |
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| Rok vydání: | 2010 |
| Předmět: |
Lipopolysaccharides
Endoplasmic Reticulum Rats Sprague-Dawley Mice Cellular and Molecular Neuroscience Stress Physiological medicine Animals RNA Small Interfering Receptor Molecular Biology Cells Cultured Pharmacology Interleukin-13 Cell Death Microglia biology Calpain Chemistry Endoplasmic reticulum Cell Biology Transfection Rats Cell biology Enzyme Activation Isoenzymes PPAR gamma Heme oxygenase medicine.anatomical_structure Biochemistry Apoptosis Unfolded protein response biology.protein Molecular Medicine Heme Oxygenase-1 |
| Zdroj: | Cellular and Molecular Life Sciences. 67:1465-1476 |
| ISSN: | 1420-9071 1420-682X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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