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KMID : 0388220120190040196
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Journal of the Korean Rheumatism Association
2012 Volume.19 No. 4 p.196 ~ p.205
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DICAM Inhibits Activation of Macrophage by Lipopolysaccharide
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Jung Youn-Kwan
Park Hye-Ri
Lee Eun-Ju
Jeong Dong-Hyoung
Kim Kun-Woo
Choi Je-Yong
Han Seung-Woo
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Abstract
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Objective: DICAM, a dual Ig domain containing adhesion molecule, is involved in cell-cell adhesion through direct interaction with ?v?3 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-? 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-?, IL-1?, and IFN-?, 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-? 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.
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KEYWORD
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DICAM, Monocyte, Macrophage, Lipopolysaccharide, RAW264.7 cells
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