title: The role of adiponectin in the production of IL-6, IL-8, VEGF and MMPs in human endothelial cells and osteoblasts: implications for arthritic joints.
abstract: This study was performed to evaluate the contribution of adiponectin to the production of interleukin (IL)-6, IL-8, vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-1 and MMP-13 in human endothelial cells and osteoblasts in arthritic joints. Cultured human umbilical vascular endothelial cells (HUVECs) and osteoblasts were stimulated with adiponectin (1 or 10 μg ml(-1)) or IL-1β (0.1 ng ml(-1)) in the presence or absence of hypoxia for 24 h. The protein expression patterns were examined by analyzing culture supernatants using the enzyme-linked immunosorbent assay (ELISA). Adiponectin significantly stimulated the production of VEGF, MMP-1 and MMP-13 in osteoblasts but not in endothelial cells, whereas it significantly stimulated the production of IL-6 and IL-8 in both endothelial cells and osteoblasts. The increase in VEGF production induced by adiponectin was significantly greater than that induced by IL-1β. The production of IL-6 and IL-8 in adiponectin-stimulated endothelial cells was approximately 10-fold higher than that in IL-1β-stimulated endothelial cells; in osteoblasts, adiponectin-induced IL-6 and IL-8 secretion was approximately twofold higher than that induced by IL-1β. In addition, IL-8 production in endothelial cells was approximately sevenfold higher than in osteoblasts. However, IL-6 levels were similar between the two cell types, suggesting that adiponectin may be involved in the production of IL-8 in endothelial cells, which may have an important role in neutrophil recruitment to arthritic joints. Furthermore, the increases in protein expression induced by adiponectin were differentially regulated by hypoxia. In conclusion, adiponectin has a more important role than does IL-1β in the production of mediators that drive synovitis and joint destruction in endothelial cells and osteoblasts at physiological concentrations.
authors.affiliation: 1] East-West Bone and Joint Research Institute, Kyung Hee University Hospital, Kyung Hee University, Seoul, Republic of Korea [2] Division of Rheumatology, Department of Internal Medicine, Kyung Hee University Medical School, Seoul, Republic of Korea.
authors.forename: Yeon-Ah
authors.initials: YA
authors.lastname: Lee
authors.affiliation: East-West Bone and Joint Research Institute, Kyung Hee University Hospital, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Hye-In
authors.initials: HI
authors.lastname: Ji
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Kyung Hee University Medical School, Seoul, Republic of Korea.
authors.forename: Sang-Hoon
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Kyung Hee University Medical School, Seoul, Republic of Korea.
authors.forename: Seung-Jae
authors.initials: SJ
authors.lastname: Hong
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Kyung Hee University Medical School, Seoul, Republic of Korea.
authors.forename: Hyung-In
authors.initials: HI
authors.lastname: Yang
authors.affiliation: East-West Bone and Joint Research Institute, Kyung Hee University Hospital, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Myung
authors.initials: M
authors.lastname: Chul Yoo
authors.affiliation: East-West Bone and Joint Research Institute, Kyung Hee University Hospital, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Kyoung Soo
authors.initials: KS
authors.lastname: Kim
mesh_terms: D052242:Adiponectin / Q000494:pharmacology / Q000502:physiology*; D001172:Arthritis, Rheumatoid / Q000378:metabolism; D015687:Cell Hypoxia; D002460:Cell Line; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism*; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D052242:Adiponectin; C508606:CXCL8 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D042461:Vascular Endothelial Growth Factor A; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1