RRC ID 41634
Author Shiojiri T, Wada K, Nakajima A, Katayama K, Shibuya A, Kudo C, Kadowaki T, Mayumi T, Yura Y, Kamisaki Y.
Title PPAR gamma ligands inhibit nitrotyrosine formation and inflammatory mediator expressions in adjuvant-induced rheumatoid arthritis mice.
Journal Eur J Pharmacol
Abstract Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor, whose activation has been linked to several physiologic pathways including those related to the regulation of insulin sensitivity. Here, we investigate effects of PPARgamma specific ligands, rosiglitazone and pioglitazone, on formation of nitrotyrosine and increased expression of inflammatory mediators such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 and intercellular adhesion molecule-1 (ICAM-1) in adjuvant-induced murine arthritis. Administration of rosiglitazone or pioglitazone (30 mg/kg, p.o.) significantly inhibited the adjuvant-induced increase in formation of nitrotyrosine and expression of iNOS on both ankle and temporomandibular joints. Rosiglitazone also inhibited the adjuvant-induced expression of M30 positive cells, as a marker of apoptosis, in the joint tissues. In addition, treatment with rosiglitazone or pioglitazone (30 microM) inhibited lipopolysaccharide plus tumor necrosis factor (TNF)-alpha-induced protein expression of iNOS, cyclooxygenase-2, ICAM-1 and nitrotyrosine formation in RAW 264 cells, a murine macrophage-like cell line. Rosiglitazone or pioglitazone inhibited increase in phosphorylated I-kappaB (pI-kappaB) expression, as an index of activation of nuclear factor (NF)-kappaB, in both joint tissues and RAW264 cells. Furthermore, in PPARgamma-transfected HEK293 cells, rosiglitazone inhibited the TNF-alpha-stimulated response using NF-kappaB-mediated transcription reporter assay. These results indicate that PPARgamma ligands may possess anti-inflammatory activity against adjuvant-induced arthritis via the inhibition of NF-kappaB pathway.
Volume 448(2-3)
Pages 231-8
Published 2002-7-19
DOI 10.1016/s0014-2999(02)01946-5
PII S0014299902019465
PMID 12144946
MeSH Animals Arthritis, Rheumatoid / chemically induced* Arthritis, Rheumatoid / drug therapy Arthritis, Rheumatoid / metabolism* Arthritis, Rheumatoid / pathology Cell Line Cyclooxygenase 2 Freund's Adjuvant Inflammation Mediators / antagonists & inhibitors* Inflammation Mediators / metabolism Isoenzymes / biosynthesis Isoenzymes / genetics Ligands Male Mice Mice, Inbred BALB C NF-kappa B / metabolism NF-kappa B / physiology Nitric Oxide Synthase / biosynthesis Nitric Oxide Synthase / genetics Nitric Oxide Synthase Type II Prostaglandin-Endoperoxide Synthases / biosynthesis Prostaglandin-Endoperoxide Synthases / genetics RNA, Messenger / antagonists & inhibitors RNA, Messenger / biosynthesis Receptors, Cytoplasmic and Nuclear / biosynthesis Receptors, Cytoplasmic and Nuclear / therapeutic use Signal Transduction / drug effects Signal Transduction / physiology Temporomandibular Joint / drug effects Temporomandibular Joint / metabolism Temporomandibular Joint / pathology Transcription Factors / biosynthesis Transcription Factors / pharmacology* Transcription Factors / therapeutic use Tyrosine / analogs & derivatives* Tyrosine / antagonists & inhibitors* Tyrosine / biosynthesis
IF 3.263
Times Cited 100
Human and Animal Cells RAW 264(RCB0535)