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        DICAM에 의한 LPS-매개 대식세포 활성화 억제

        정연관 ( Youn Kwan Jung ),박혜리 ( Hye Ri Park ),이은주 ( Eun Ju Lee ),정동형 ( Dong Hyoung Jeong ),김건우 ( Gun Woo Kim ),최제용 ( Je Yong Choi ),한승우 ( Seung Woo Han ) 대한류마티스학회 2012 대한류마티스학회지 Vol.19 No.4

        DICAM, a dual Ig domain containing adhesion molecule, is involved in cell-cell adhesion through direct interaction with αvβ3 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-a 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-α, IL-1β, and IFN-γ, 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-α 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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