title: Increased autophagy in fibroblast-like synoviocytes leads to immune enhancement potential in rheumatoid arthritis.
abstract: The incidence of rheumatoid arthritis (RA) has been reported to be correlated with a disorder of immunregulation. Rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs) play an important role in regulating the local immune microenvironment. However, the potential mechanism of RA-FLS in regulating the immnue response is not clearly understood. In this study, we demonstrated that the expression of HIF-1α was significantly up-regulated in rheumatoid arthritis tissue which indicated that the hypoxia condition in the microenvironment. We also observed that RA-FLSs demonstrated the potential to up-regulate immune activation. Meanwhile, the level of autophagy increased in RA-FLSs compared with control group. Besides that, the expression of IL-6 was up-regulated not only in RA-FLSs but also in the fibroblasts that treated with hypoxia condition. Accordingly, we found that autophagy inhibitiors could effectively inhibit the immune activation function of RA-FLSs medicated by IL-6. Taken together, the results we demonstrated above indicated that the hypoxia microenvironment could effectively induce the incidence of autophagy and then lead to the immune activation function of RA-FLSs medicated by IL-6.
authors.affiliation: Department of Rheumatology, The Second Affiliated Hospital to Soochow University, Jiangsu, China.
authors.forename: Ru
authors.initials: R
authors.lastname: Yang
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital to Soochow University, Jiangsu, China.
authors.forename: Yingzi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital to Soochow University, Jiangsu, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, The Second Affiliated Hospital to Soochow University, Jiangsu, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Rheumatology, The Second Affiliated Hospital to Soochow University, Jiangsu, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wen
authors.affiliation: Department of Rheumatology, The Second Affiliated Hospital to Soochow University, Jiangsu, China.
authors.forename: Leixi
authors.initials: L
authors.lastname: Xue
authors.affiliation: Department of Rheumatology, The Second Affiliated Hospital to Soochow University, Jiangsu, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Tang
authors.affiliation: Department of Rheumatology, The Second Affiliated Hospital to Soochow University, Jiangsu, China.
authors.forename: Zhichun
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Hematology, The Second Affiliated Hospital to Soochow University, Jiangsu, China.
authors.forename: Jinxiang
authors.initials: J
authors.lastname: Fu
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D015153:Blotting, Western; D015687:Cell Hypoxia; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000070918:Synoviocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
chemical_list: D018501:Antirheumatic Agents; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D015850:Interleukin-6; C025946:3-methyladenine; D002738:Chloroquine; D000225:Adenine
keywords: IL-6; autophagy; fibroblast-like synoviocytes; rheumatoid arthritis