DICAM Inhibits Activation of Macrophage by Lipopolysaccharide.
10.4078/jrd.2012.19.4.196
- Author:
Youn Kwan JUNG
1
;
Hye Ri PARK
;
Eun Ju LEE
;
Dong Hyoung JEONG
;
Gun Woo KIM
;
Je Yong CHOI
;
Seung Woo HAN
Author Information
1. Laboratory for Arthritis and Bone Biology, Fatima Research Institute, Daegu Fatima Hospital, Daegu, Korea. kiefe73@gmail.com
- Publication Type:Original Article
- Keywords:
DICAM;
Monocyte;
Macrophage;
Lipopolysaccharide;
RAW264.7 cells
- MeSH:
Arthritis, Experimental;
Cell Line;
Cytokines;
Inflammation Mediators;
Macrophage Activation;
Macrophage Colony-Stimulating Factor;
Macrophages;
Monocytes;
Osteoclasts;
Phosphorylation;
Phosphotransferases;
Tumor Necrosis Factor-alpha
- From:Journal of Rheumatic Diseases
2012;19(4):196-205
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
OBJECTIVE: DICAM, a dual Ig domain containing adhesion molecule, is involved in cell-cell adhesion through direct interaction with alphavbeta3 integrin. In our previous study showing the inhibitory role of DICAM in osteoclast differentiation, we found that DICAM also has a suppressive role in macrophage, the precursor cell of osteoclast. The role of DICAM in macrophage activation at the inflammatory milieu, however, remains obscure. METHODS: Expression pattern of DICAM by inflammatory cytokines and lipopolysaccharide (LPS) was studied with RAW264.7, a murine macrophage cell line. To study the role of DICAM on macrophage activation, we stably transduced DICAM, or empty vector, into RAW264.7, and then compared the LPS-mediated activation such as spreading and TNF-alpha production. RESULTS: DICAM was abundantly expressed in the synovial tissue of collagen-induced arthritis. When we assessed the expression of DICAM in RAW264.7 cells by mediators of inflammation, inflammatory cytokines, such as TNF-alpha, IL-1beta, and IFN-gamma, and M-CSF increased the expression of DICAM; however, LPS decreased. Functionally, DICAM that stably transduced-RAW264.7 cells showed attenuation of LPS-mediated macrophage activation including spreading and TNF-alpha production. DICAM decreased the phosphorylation of JNK MAP kinase by M-CSF and LPS stimulation, which was corroborated by a decrease in the expression of ITAM-associated receptors including Trem2, Pira1, and Oscar. Finally, a recombinant ectodomain of DICAM suppressed LPS-induced activation of RAW264.7 cells. CONCLUSION: These results indicate that DICAM acts as a negative regulator of LPS-mediated macrophage activation.
