The anti-allergic compound tranilast attenuates inflammation and inhibits bone destruction in collagen-induced arthritis in mice.

Abstract

BACKGROUND AND PURPOSE:

Recent findings suggest the importance of mast cells in the pathogenesis of rheumatoid arthritis and their potential as a therapeutic target. Tranilast is an anti-allergic compound with a potent membrane-stabilizing effect on mast cells and a wide range of anti-inflammatory effects, thus may be advantageous in the treatment of arthritis. Here, we have evaluated the effects of tranilast on the progression of collagen-induced arthritis in mice.

EXPERIMENTAL APPROACH:

Tranilast (400 mg.kg(-1).day(-1)) was orally administered for 8 weeks to mice with established collagen-induced arthritis. Arthritis was assessed by clinical signs and X-ray scores. In paw tissue, the numbers of mast cells and osteoclasts were measured by histological analysis, and several inflammatory factors were assessed by RT-PCR and Western blot analysis.*

KEY RESULTS:

TNF-alpha-positive mast cells were present extensively throughout the inflamed synovium of vehicle-treated arthritic mice, with some mast cells in close proximity to osteoclasts in areas of marked bone and cartilage destruction. Tranilast significantly reduced clinical and X-ray scores of arthritis and decreased numbers of TNF-alpha-positive mast cells and mRNA levels of TNF-alpha, chymase (mouse mast cell protease 4), tryptase (mouse mast cell protease 6), stem cell factor, interleukin-6, cathepsin-K, receptor activator of nuclear factor-kappaB, and of receptor activator of nuclear factor-kappaB-ligand, but increased interleukin-10 mRNA level in paws of arthritic mice. Osteoclast numbers were decreased by treatment with tranilast.

CONCLUSIONS AND IMPLICATIONS:

Tranilast possesses significant anti-rheumatic efficacy and, probably, this therapeutic effect is partly mediated by inhibition of mast cell activation and osteoclastogenesis.

• Authors: N Shiota, P T Kovanen, K K Eklund, N Shibata, K Shimoura, T Niibayashi, C Shimbori, H Okunishi
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 159 Issue 3 Pg. 626-35 (Feb 01 2010) ISSN: 1476-5381 [Electronic] England
• PMID: 20067475 (Publication Type: Journal Article)

Chemical References

• Anti-Allergic Agents
• Carrier Proteins
• Interleukin-6
• Oligonucleotides
• RANK Ligand
• Receptor Activator of Nuclear Factor-kappa B
• Stem Cell Factor
• Tumor Necrosis Factor-alpha
• ortho-Aminobenzoates
• phosphodiester alpha
• Interleukin-10
• tranilast

Topics

• Animals
• Anti-Allergic Agents (adverse effects, pharmacology, therapeutic use)
• Arthritis, Experimental (chemically induced, drug therapy, pathology)
• Arthritis, Rheumatoid (drug therapy, pathology)
• Bone and Bones (metabolism, pathology)
• Carrier Proteins (genetics, pharmacology, therapeutic use)
• Cartilage (drug effects, metabolism, pathology)
• Inflammation (drug therapy, pathology)
• Interleukin-10 (genetics, pharmacology, therapeutic use)
• Interleukin-6 (genetics, pharmacology, therapeutic use)
• Male
• Mast Cells (metabolism, pathology)
• Mice
• Mice, Inbred DBA
• Oligonucleotides
• Osteoclasts (drug effects, metabolism, pathology)
• RANK Ligand (genetics, pharmacology)
• Receptor Activator of Nuclear Factor-kappa B (genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Stem Cell Factor (genetics, pharmacology, therapeutic use)
• Synovial Membrane (metabolism, pathology)
• Tumor Necrosis Factor-alpha (genetics, pharmacology, therapeutic use)
• X-Rays
• ortho-Aminobenzoates