title: Pim-2/mTORC1 Pathway Shapes Inflammatory Capacity in Rheumatoid Arthritis Synovial Cells Exposed to Lipid Peroxidations.
abstract: Rheumatoid arthritis is a systemic autoimmune disease characterized by chronic inflammation of multiple joints, with disruption of joint cartilage. The proliferation of synovial fibroblasts in response to multiple inflammation factors is central to the pathogenesis of rheumatoid arthritis. Our previous studies showed that 4-HNE may induce synovial intrinsic inflammations by activating NF-κB pathways and lead to cell apoptosis. However, the molecular mechanisms of how synovial NF-κB activation is modulated are not fully understood. Here, the present findings demonstrated that 4-HNE may induce synovial intrinsic inflammations by mTORC1 inactivation. While ectopic activation of mTORC1 pathway by the overexpression of Pim-2 may disrupt the initiation of inflammatory reactions and maintain synovial homeostasis, our findings will help to uncover novel signaling pathways between inflammations and oxidative stress in rheumatoid arthritis development and imply that Pim-2/mTORC1 pathway may be critical for the initiation of inflammatory reactions in human rheumatoid arthritis synovial cells.
authors.affiliation: Department of Rheumatology and Immunology, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Geng
authors.initials: G
authors.lastname: Yin
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital of Xiamen University, No. 55, Zhenhai Road, Xiamen, Fujian 361003, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Rheumatology and Immunology, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Rheumatology and Immunology, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Xiao-min
authors.initials: XM
authors.lastname: Cen
authors.affiliation: Department of Rheumatology and Immunology, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Qi-bing
authors.initials: QB
authors.lastname: Xie
mesh_terms: D000447:Aldehydes / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects*; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000037:antagonists & inhibitors; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D013582:Synovial Fluid / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000447:Aldehydes; D046912:Multiprotein Complexes; D016328:NF-kappa B; C490587:PIM2 protein, human; D011518:Proto-Oncogene Proteins; D014409:Tumor Necrosis Factor-alpha; D000076222:Mechanistic Target of Rapamycin Complex 1; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases; C027576:4-hydroxy-2-nonenal