Suppressive role of leukocyte cell-derived chemotaxin 2 in mouse anti-type II collagen antibody-induced arthritis.

Abstract

OBJECTIVE:

We previously reported that the Val58Ile polymorphism of the leukocyte cell-derived chemotaxin 2 gene (LECT2) is associated with the severity of rheumatoid arthritis (RA). To define the role of LECT2 in inflammatory arthritides, we investigated the development of collagen antibody-induced arthritis (CAIA) in LECT2-deficient (LECT2(-/-)) mice.

METHODS:

CAIA was induced in mice by administering anti-type II collagen antibodies followed by lipopolysaccharide. Daily assessment of hind paw swelling was used to monitor the development of arthritis. The histopathologic features and expression of inflammatory cytokines were also analyzed. We confirmed the role of LECT2 by introducing a LECT2 expression vector into LECT2(-/-) mice, using a hydrodynamic gene transfer method.

RESULTS:

Arthritis in LECT2(-/-) mice was significantly exacerbated compared with that in wild-type (WT) controls. Histopathologic assessment of the tarsal joints showed that inflammation and erosion of cartilage and bone in LECT2(-/-) mice were more severe than that in controls. Interleukin-1beta (IL-1beta), IL-6, and certain chemokines were present at significantly higher levels in the arthritic hind paws of LECT2(-/-) mice. In contrast, the amount of LECT2 in the serum and locally in the hind paws was higher in arthritic WT mice. Finally, hydrodynamic gene transfer experiments revealed that the severity of arthritis was reduced by the systemic expression of exogenous mouse LECT2 protein in LECT2(-/-) mice.

CONCLUSION:

These results strongly suggest that LECT2 directly suppresses the development of CAIA. Manipulation of LECT2 might provide a rationale for novel therapeutic approaches to the treatment of inflammatory arthritides such as RA.

• Authors: Akinori Okumura, Takeshi Saito, Isao Otani, Kazuo Kojima, Yasunori Yamada, Akiko Ishida-Okawara, Katsuyoshi Nakazato, Masahide Asano, Kiichi Kanayama, Yoichiro Iwakura, Kazuo Suzuki, Satoshi Yamagoe
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 58 Issue 2 Pg. 413-21 (Feb 2008) ISSN: 0004-3591 [Print] United States
• PMID: 18240267 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantibodies
• Chemokine CCL3
• Intercellular Signaling Peptides and Proteins
• Interleukin-1beta
• Lect2 protein, mouse
• Lipopolysaccharides
• Tumor Necrosis Factor-alpha

Topics

• Animals
• Arthritis, Experimental (genetics, immunology, pathology)
• Autoantibodies (pharmacology)
• Chemokine CCL3 (immunology)
• Gene Expression (immunology)
• Intercellular Signaling Peptides and Proteins (genetics, immunology)
• Interleukin-1beta (immunology)
• Lipopolysaccharides (pharmacology)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Mutant Strains
• Polymorphism, Genetic
• Tarsal Joints (pathology)
• Tumor Necrosis Factor-alpha (immunology)