Galectin‐3 deficiency protects lipopolysaccharide‐induced chondrocytes injury via regulation of TLR4 and PPAR‐γ‐mediated NF‐κB signaling pathway
| Autor: | Xue-dong Li, Peng Xie, Jing-ming Han, Wei‐wei Xiao, Gui-zhou Zheng, Shi-xin Du, Jian‑Sheng Wang, Yong-Sheng Zhong |
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| Rok vydání: | 2018 |
| Předmět: |
Lipopolysaccharides
0301 basic medicine Galectin 3 Apoptosis Inflammation Biochemistry 03 medical and health sciences chemistry.chemical_compound Chondrocytes 0302 clinical medicine Downregulation and upregulation Cell Line Tumor Matrix Metalloproteinase 13 Osteoarthritis medicine Animals Anilides Molecular Biology Chemistry NF-kappa B Interleukin NF-κB Cell Biology Cell biology PPAR gamma Toll-Like Receptor 4 030104 developmental biology 030220 oncology & carcinogenesis TLR4 Cytokines RNA Interference lipids (amino acids peptides and proteins) Tumor necrosis factor alpha Inflammation Mediators Matrix Metalloproteinase 1 medicine.symptom Signal transduction Apoptosis Regulatory Proteins Signal Transduction |
| Zdroj: | Journal of Cellular Biochemistry. 120:10195-10204 |
| ISSN: | 1097-4644 0730-2312 |
| DOI: | 10.1002/jcb.28304 |
| Popis: | The aim of the present study was to identify the functional role of galectin-3 (Gal-3) in lipopolysaccharide (LPS)-induced injury in ATDC5 cells and to explore the probable molecular mechanisms. Here, we identified that LPS is sufficient to enhance the expression of Gal-3 in ATDC5 cells. In addition, repression of Gal-3 obviously impeded LPS-stimulated inflammation damage as exemplified by a reduction in the release of inflammatory mediators interleukin (IL)-1β, IL-6, and tumor necrosis factor-α, as well as the production of nitric oxide and prostaglandin E2 (PGE2) concomitant with the downregulation of matrix metalloproteinases (MMP)-13 and MMP-3 expression in ATDC5 cells after LPS administration. Moreover, ablation of Gal-3 dramatically augmented cell ability and attenuated cell apoptosis accompanied by an increase in the expression of antiapoptotic protein Bcl-2 and a decrease in the expression of proapoptotic protein Bax and caspase-3 in ATDC5 cells subjected with LPS. Importantly, we observed that forced expression of TLR4 or blocked PPAR-γ with the antagonist GW9662 effectively abolished Gal-3 inhibition-mediated anti-inflammatory and antiapoptosis effects triggered by LPS. Mechanistically, depletion of Gal-3 prevents the NF-κB signaling pathway. Taken together, these findings indicated that the absence of Gal-3 exerted chondroprotective properties dependent on TLR4 and PPAR-γ-mediated NF-κB signaling, indicating that Gal-3 functions as a protector in the development and progression of osteoarthritis. |
| Databáze: | OpenAIRE |
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