title: α-Lipoic acid (α-LA) inhibits the transcriptional activity of interferon regulatory factor 1 (IRF-1) via SUMOylation.
abstract: Osteoarthritis (OA), one of the most common joint disorders, is one of the leading causes of disability among the elderly. Proinflammatory cytokines, such as interleukin (IL)-1β, which is synthesized locally by synovial cells and chondrocytes, have been shown to play a critical role in sustaining cartilage damage in arthritis by creating an imbalance between cartilage degradation and the repair process. Alpha-lipoic acid (α-LA), which is synthesized in animal and plant tissues, has demonstrated its protective effects in a variety of diseases. However, whether or not LA has a protective effect in OA is still unknown. In this study, we found that α-LA inhibits the IL-1β-induced increase in matrix metallopeptidase 3 (MMP-3) and matrix metallopeptidase 13 (MMP-13) expression and activity. Our data also demonstrate that interferon regulatory factor 1 (IRF-1) participates in the induction of MMP-3 and MMP-13. However, α-LA treatment did not change IRF-1 levels. Importantly, we found that α-LA increases SUMOylation of IRF-1, which attenuates IRF-1's transcriptional activity. Finally, we found that α-LA treatment leads to an increase in SUMO-1, but not in SUMO-2 or SUMO-3. Taken together, this study shows that α-LA exerts anti-inflammatory effects in an IL-1β-stimulated chondrocyte model, thereby suggesting a potential protective effect of α-LA in OA.
authors: Department of Orthopedics, Yantaishan Hospital, Yantai 264025, Shandong Province, China.
authors: Tao
authors: T
authors: Sun
authors: Department of Orthopedics, Yantaishan Hospital, Yantai 264025, Shandong Province, China.
authors: Fuyu
authors: F
authors: Gao
authors: Department of Endocrine, Yantai Zhifu Hospital, Yantai 2960319, Shandong Province, China.
authors: Xiaoyan
authors: X
authors: Lin
authors: Department of Endocrine, Yantaishan Hospital, Yantai 264025, Shandong Province, China.
authors: Ruixiang
authors: R
authors: Yu
authors: Department of Orthopedics, Yantaishan Hospital, Yantai 264025, Shandong Province, China.
authors: Yong
authors: Y
authors: Zhao
authors: Department of Orthopedics, Yantaishan Hospital, Yantai 264025, Shandong Province, China.
authors: Jingjie
authors: J
authors: Luan
authors: Department of Orthopedics, Yantaishan Hospital, Yantai 264025, Shandong Province, China.
authors: Hongyan
authors: H
authors: Li
authors: Department of Orthopedics, Yantaishan Hospital, Yantai 264025, Shandong Province, China. Electronic address: songmz866@hotmail.com.
authors: Mingzhu
authors: M
authors: Song
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000378:metabolism*; D053583:Interleukin-1beta / Q000494:pharmacology; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D010003:Osteoarthritis / Q000378:metabolism; D025842:SUMO-1 Protein / Q000378:metabolism; D058207:Sumoylation; D008063:Thioctic Acid / Q000494:pharmacology*; D014158:Transcription, Genetic
chemical_list: C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D053583:Interleukin-1beta; D025842:SUMO-1 Protein; C495501:SUMO1 protein, human; D008063:Thioctic Acid; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3
keywords: Chondrocyte; Interferon regulatory factor 1; Interleukin (IL)-1β; Lipoic acid; Osteoarthritis; SUMOylation