Thymic stromal lymphopoietin secretion of synovial fibroblasts is positively and negatively regulated by Toll-like receptors/nuclear factor-kappaB pathway and interferon-gamma/dexamethasone

Tetsuro Ozawa; Kensuke Koyama; Takashi Ando; Yuko Ohnuma; Kyosuke Hatsushika; Tetsuro Ohba; Hajime Sugiyama; Yoshiki Hamada; Hideoki Ogawa; Ko Okumura; Atsuhito Nakao

doi:10.1007/s10165-007-0620-9

Thymic stromal lymphopoietin secretion of synovial fibroblasts is positively and negatively regulated by Toll-like receptors/nuclear factor-kappaB pathway and interferon-gamma/dexamethasone

Mod Rheumatol. 2007;17(6):459-63. doi: 10.1007/s10165-007-0620-9. Epub 2007 Dec 20.

Authors

Tetsuro Ozawa¹, Kensuke Koyama, Takashi Ando, Yuko Ohnuma, Kyosuke Hatsushika, Tetsuro Ohba, Hajime Sugiyama, Yoshiki Hamada, Hideoki Ogawa, Ko Okumura, Atsuhito Nakao

Affiliation

¹ Department of Immunology, Faculty of Medicine, University of Yamanashi, Chuo, Japan. [email protected]

PMID: 18084696
DOI: 10.1007/s10165-007-0620-9

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Arthritis, Rheumatoid / metabolism
Benzamides / pharmacology
Cell Survival / drug effects
Cells, Cultured
Culture Media, Conditioned / chemistry
Culture Media, Conditioned / metabolism
Cytokines / metabolism*
Dexamethasone / pharmacology
Dose-Response Relationship, Drug
Female
Fibroblasts / drug effects
Fibroblasts / metabolism*
Humans
Interferon-gamma / pharmacology
Ligands
Lipopolysaccharides / pharmacology
Male
NF-kappa B / metabolism
Osteoarthritis, Knee / metabolism
Poly I-C / pharmacology
Recombinant Proteins
Stromal Cells / metabolism*
Synovial Membrane / drug effects
Synovial Membrane / metabolism*
Thymic Stromal Lymphopoietin
Toll-Like Receptors / metabolism
Up-Regulation

Substances

Benzamides
Culture Media, Conditioned
Cytokines
Ligands
Lipopolysaccharides
NF-kappa B
Recombinant Proteins
Toll-Like Receptors
N-(3,5-bis(trifluoromethyl)phenyl)-5-chloro-2-hydroxybenzamide
Dexamethasone
Interferon-gamma
Poly I-C
Thymic Stromal Lymphopoietin