Thymic stromal lymphopoietin secretion of synovial fibroblasts is positively and negatively regulated by Toll-like receptors/nuclear factor-kappaB pathway and interferon-gamma/dexamethasone.
Thymic stromal lymphopoietin (TSLP) is an interleukin (IL)-7-like cytokine produced by epithelial cells and triggers dendritic cell-mediated Th2 type allergic inflammatory responses. This study investigated whether Toll-like receptor (TLR) ligands, lipopolysaccharide (LPS) and poly-IC affect TSLP production in synovial fibroblasts. Enzyme-linked immunosorbent assay showed that LPS and poly-IC upregulated TSLP production in synovial fibroblasts obtained from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). In addition, we found that nuclear factor (NF)-kappaB inhibitor IMD-0354, dexamethasone, and interferon (IFN)-gamma inhibited the LPS- and poly-IC-induced TSLP production in RA and OA synovial fibroblasts. Thus, LPS and poly-IC can upregulate TSLP via a NF-kappaB pathway in synovial fibroblasts, which is downregulated by dexamethasone and interferon (IFN)-gamma. The current findings suggest that TSLP may be involved in the pathophysiology of inflammatory arthritis as well as allergic disease.
Ozawa
Tetsuro
T
Department of Immunology, Faculty of Medicine, University of Yamanashi, Chuo, Japan. vesupanomusuko@yahoo.co.jp
Koyama
Kensuke
K
Ando
Takashi
T
Ohnuma
Yuko
Y
Hatsushika
Kyosuke
K
Ohba
Tetsuro
T
Sugiyama
Hajime
H
Hamada
Yoshiki
Y
Ogawa
Hideoki
H
Okumura
Ko
K
Nakao
Atsuhito
A
D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000378:metabolism; D001549:Benzamides / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D020370:Osteoarthritis, Knee / Q000378:metabolism; D011070:Poly I-C / Q000494:pharmacology; D011994:Recombinant Proteins; D017154:Stromal Cells / Q000378:metabolism*; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism*; D051193:Toll-Like Receptors / Q000378:metabolism; D015854:Up-Regulation; D000094632:Thymic Stromal Lymphopoietin
D001549:Benzamides; D017077:Culture Media, Conditioned; D016207:Cytokines; D008024:Ligands; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011994:Recombinant Proteins; D051193:Toll-Like Receptors; C492919:N-(3,5-bis(trifluoromethyl)phenyl)-5-chloro-2-hydroxybenzamide; D003907:Dexamethasone; D007371:Interferon-gamma; D011070:Poly I-C; D000094632:Thymic Stromal Lymphopoietin