Tumor necrosis factor-alpha increases chemokine gene expression and production in synovial fibroblasts from human temporomandibular joint.
BACKGROUND
Synovitis, which is characterized by infiltration of inflammatory cells, often accompanies progression of clinical symptoms of the temporomandibular joint (TMJ). Synovial fibroblasts of the TMJ are believed to play important roles in progression of synovitis. The purpose of this study was to examine production and gene expression of chemokines by synovial fibroblasts stimulated by tumor necrosis factor-alpha (TNF-alpha).


METHODS
Protein levels of chemokines were measured by enzyme-linked immunosorbent assay (ELISA). Gene expression of chemokines was analyzed by real-time polymerase chain reaction (PCR).


RESULTS
Production of interleukin (IL)-8, growth-related oncogene (GRO)-alpha, monocyte chemoattractant protein (MCP)-1, and regulated upon activation normal T-cell expressed and secreted (RANTES) protein by synovial fibroblasts was increased by TNF-alpha. In contrast, stromal cell-derived factor (SDF)-1alpha, macrophage inflammatory protein (MIP)-1alpha and -1beta were not detectable in conditioned media of synovial fibroblasts, with or without TNF-alpha treatment. Increases in gene expression of IL-8, GRO-alpha, MCP-1, and RANTES in response to TNF-alpha treatment were detected.


CONCLUSIONS
Increased protein production and gene expression of chemokines by synovial fibroblasts in response to TNF-alpha treatment appears to play an important role in recruitment of inflammatory cells into synovium and the progression of synovitis in the TMJ.
Ogura
Naomi
N
Department of Oral Surgery, Nihon University School of Dentistry at Matsudo, Chiba, Japan.
Tobe
Makiko
M
Sakamaki
Hiroyuki
H
Nagura
Hideaki
H
Abiko
Yoshimitsu
Y
Kondoh
Toshirou
T
D000293:Adolescent; D000328:Adult; D018932:Chemokine CCL2 / Q000032:analysis / Q000187:drug effects / Q000235:genetics; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000032:analysis / Q000235:genetics; D054360:Chemokine CXCL1; D054377:Chemokine CXCL12; D018925:Chemokines / Q000032:analysis* / Q000235:genetics; D019743:Chemokines, CXC / Q000032:analysis / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis / Q000235:genetics; D016209:Interleukin-8 / Q000032:analysis / Q000235:genetics; D004204:Joint Dislocations / Q000276:immunology / Q000473:pathology; D019402:Macrophage Inflammatory Proteins / Q000032:analysis / Q000235:genetics; D010003:Osteoarthritis / Q000276:immunology / Q000473:pathology; D013583:Synovial Membrane / Q000187:drug effects* / Q000276:immunology; D013585:Synovitis / Q000276:immunology / Q000473:pathology; D019224:Temporomandibular Joint Disc / Q000276:immunology / Q000473:pathology; D013705:Temporomandibular Joint Disorders / Q000276:immunology / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
C475829:CXCL1 protein, human; C515255:CXCL12 protein, human; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D054360:Chemokine CXCL1; D054377:Chemokine CXCL12; D018925:Chemokines; D019743:Chemokines, CXC; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8; D019402:Macrophage Inflammatory Proteins; D014409:Tumor Necrosis Factor-alpha