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.
Subject(s)
Arthritis, Experimental , Cell Line , Cytokines , Inflammation Mediators , Macrophage Activation , Macrophage Colony-Stimulating Factor , Macrophages , Monocytes , Osteoclasts , Phosphorylation , Phosphotransferases , Tumor Necrosis Factor-alphaABSTRACT
Intrathecal chemotherapy with methotrexate and cytarabine arabinoside is used for the treatment and prophylaxis of malignancies, but can induce myelopathy. We report the case of a 50-year-old woman with stomach cancer who developed myelopathy after administration of intrathecal cytarabine arabinoside and methotrexate. The patient's neurologic status improved rapidly after the administration of folinate (15 mg) four times daily and cyanocobalamin (100 mug) once daily. The folate metabolites may be effective in the management of intrathecal-chemotherapy-induced myelopathy.