Synoviocyte-derived angiopoietin-like protein 2 contributes to synovial chronic inflammation in rheumatoid arthritis.

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by symmetrical polyarticular synovitis of the diarthrodial joints. Several proinflammatory cytokines derived from both infiltrating inflammatory cells and activated resident cells within the RA joint play a fundamental role in the processes that cause inflammation. However, anticytokine treatment is beneficial but not curative, the effects are only partial, and nonresponses are common. Therefore, an effort has been made to identify other key regulators of inflammation in articular structures to develop new therapies to suppress synovial inflammation and joint destruction in RA. Adipose tissue-derived angiopoietin-like protein 2 (Angptl2) activates an inflammatory cascade in endothelial cells and induces chemotaxis of monocytes/macrophages in obesity, resulting in initiation and propagation of inflammation within adipose tissues and obesity-related metabolic diseases. Angptl2 mRNA and protein are abundantly expressed in hyperplastic rheumatoid synovium of RA patients, especially in fibroblast-like and macrophage-like synoviocytes, but not in B and T lymphocytes. Angptl2 concentration in joints of RA patients was also significantly increased in comparison with patients with osteoarthritis, which in comparison with RA represents a significantly lower inflammatory grade form of arthritis. Notably, Angptl2 promoted increased chemotactic activities of CD14+CD16- monocytes from synovial fluid of RA patients. Therefore, Angptl2 acts as an important rheumatoid synovium-derived inflammatory mediator in RA pathogenesis.

• Authors: Tatsuya Okada, Hiroto Tsukano, Motoyoshi Endo, Mitsuhisa Tabata, Keishi Miyata, Tsuyoshi Kadomatsu, Kazuya Miyashita, Kei Semba, Eiichi Nakamura, Michishi Tsukano, Hiroshi Mizuta, Yuichi Oike
• Journal: The American journal of pathology (Am J Pathol) Vol. 176 Issue 5 Pg. 2309-19 (May 2010) ISSN: 1525-2191 [Electronic] United States
• PMID: 20304962 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ANGPTL2 protein, human
• Angiopoietin-Like Protein 2
• Angiopoietin-like Proteins
• Angiopoietins
• Lipopolysaccharide Receptors
• RNA, Messenger
• Receptors, IgG

Topics

• Adult
• Aged
• Angiopoietin-Like Protein 2
• Angiopoietin-like Proteins
• Angiopoietins (metabolism)
• Arthritis, Rheumatoid (metabolism)
• Chronic Disease
• Female
• Humans
• Inflammation
• Lipopolysaccharide Receptors (biosynthesis)
• Male
• Middle Aged
• Osteoarthritis (metabolism)
• RNA, Messenger (metabolism)
• Receptors, IgG (biosynthesis)
• Synovial Membrane (cytology, pathology)