RRC ID 63459
Author Chien SY, Huang CY, Tsai CH, Wang SW, Lin YM, Tang CH.
Title Interleukin-1β induces fibroblast growth factor 2 expression and subsequently promotes endothelial progenitor cell angiogenesis in chondrocytes.
Journal Clin Sci (Lond)
Abstract Arthritis is a process of chronic inflammation that results in joint damage. IL (interleukin)-1β is an inflammatory cytokine that acts as a key mediator of cartilage degradation, and is abundantly expressed in arthritis. Neovascularization is one of the pathological characteristics of arthritis. However, the role of IL-1β in the angiogenesis of chondrocytes remains unknown. In the present study, we demonstrate that stimulating chondrocytes (ATDC5) with IL-1β increased the expression of FGF (fibroblast growth factor)-2, a potent angiogenic inducer, and then promoted EPC (endothelial progenitor cell) tube formation and migration. In addition, FGF-2-neutralizing antibody abolished ATDC5-conditional medium-mediated angiogenesis in vitro, as well as its angiogenic effects in the CAM (chick chorioallantoic membrane) assay and Matrigel plug nude mice model in vivo. IHC (immunohistochemistry) staining from a CIA (collagen-induced arthritis) mouse model also demonstrates that arthritis increased the expression of IL-1β and FGF-2, as well as EPC homing in articular cartilage. Moreover, IL-1β-induced FGF-2 expression via IL-1RI (type-1 IL-1 receptor), ROS (reactive oxygen species) generation, AMPK (AMP-activated protein kinase), p38 and NF-κB (nuclear factor κB) pathway has been demonstrated. On the basis of these findings, we conclude that IL-1β promotes FGF-2 expression in chondrocytes through the ROS/AMPK/p38/NF-κB signalling pathway and subsequently increases EPC angiogenesis. Therefore IL-1β serves as a link between inflammation and angiogenesis during arthritis.
Volume 130(9)
Pages 667-81
Published 2016-5-1
DOI 10.1042/CS20150622
PII CS20150622
PMID 26811540
PMC PMC4797417
MeSH AMP-Activated Protein Kinases / metabolism Animals Arthritis, Experimental / metabolism Arthritis, Experimental / pathology Cell Line Chickens Chondrocytes / cytology* Chondrocytes / drug effects Chondrocytes / metabolism Disease Models, Animal Endothelial Progenitor Cells / drug effects Endothelial Progenitor Cells / metabolism* Enzyme Activation / drug effects Fibroblast Growth Factor 2 / metabolism* Humans Interleukin-1beta / pharmacology* Joints / drug effects Joints / pathology Male Mice Mice, Inbred C57BL NF-kappa B / metabolism Neovascularization, Physiologic / drug effects* Reactive Oxygen Species / metabolism Receptors, Interleukin / metabolism p38 Mitogen-Activated Protein Kinases / metabolism
IF 5.223
Human and Animal Cells ATDC5(RCB0565)