Involvement of tachykinins and NK1 receptor in the joint inflammation with collagen type II-specific monoclonal antibody-induced arthritis in mice.

Abstract

Rheumatoid arthritis (RA) is a chronic multisystem disease characterized by persistent joint inflammation associated with severe pain. Because RA is an immune-mediated joint disease and because type II collagen is considered an autoantigen, rodent models of arthritis using collagen type II-specific monoclonal antibodies are valuable for studying the pathogenesis of autoimmune arthritis and for evaluating therapeutic strategies. The tachykinin family peptides, substance P (SP) and hemokinin-1 (HK-1), are expressed in the nervous systems and in many peripheral organs and immunocompetent cells and activate tachykinin NK1 receptors with similar affinities. NK1 receptors are involved in the inflammation and hyperalgesia associated with a variety of inflammatory diseases. In the present study, we examined the involvement of SP and HK-1 in the joint inflammation and hyperalgesia in a collagen antibody-induced arthritis (CAIA) model in mice. The messenger RNA expression levels of the TAC1 gene encoding SP and of the TAC4 gene encoding HK-1 were decreased in the dorsal root ganglia and spinal cord at the peak of the inflammatory symptoms in CAIA. Systemic injection of an NK1 receptor antagonist, WIN 51708, significantly inhibited the joint swelling, but not the mechanical allodynia, on day 7 in CAIA mice. The messenger RNA expression levels of TAC1 and TAC4 in the dorsal root ganglia and dorsal spinal cord were unaffected by treatment with WIN 51708. These findings suggest that tachykinins and NK1 receptors play a key role in joint inflammation, rather than in nociceptive sensitization, in CAIA.

• Authors: Akira Makino, Atsushi Sakai, Hiromoto Ito, Hidenori Suzuki
• Journal: Journal of Nippon Medical School = Nippon Ika Daigaku zasshi (J Nippon Med Sch) Vol. 79 Issue 2 Pg. 129-38 ( 2012) ISSN: 1347-3409 [Electronic] Japan
• PMID: 22687356 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Androstanes
• Antibodies, Monoclonal
• Benzimidazoles
• Collagen Type II
• Protein Precursors
• RNA, Messenger
• Receptors, Neurokinin-1
• Tac4 protein, mouse
• Tachykinins
• WIN 51708
• Indomethacin

Topics

• Androstanes (pharmacology)
• Animals
• Antibodies, Monoclonal
• Arthritis, Experimental (genetics, metabolism, pathology)
• Benzimidazoles (pharmacology)
• Collagen Type II (immunology)
• Ganglia, Spinal (drug effects, metabolism, pathology)
• Gene Expression Regulation (drug effects)
• Hyperalgesia (complications, genetics, pathology)
• Indomethacin (pharmacology)
• Inflammation (complications, genetics, pathology)
• Joints (drug effects, pathology)
• Male
• Mice
• Mice, Inbred DBA
• Protein Precursors (genetics, metabolism)
• RNA, Messenger (genetics, metabolism)
• Receptors, Neurokinin-1 (metabolism)
• Spinal Cord (drug effects, metabolism, pathology)
• Tachykinins (genetics, metabolism)
• Time Factors