Cytoplasmic Domain of Intercellular Adhesion Molecule-1(ICAM-1)is Important for the ICAM-1 Mediated Membrane Projection of Endothelial Cells / 대한해부학회지

Intercellular adhesion molecule-1 (ICAM-1)has been shown to enhance leukocyte adhesion, thereby inducing migration through blood endothelial cells. However, the molecular event during the process of adhesion is largely unknown. To examine the role of ICAM-1 cytoplasmic domain in SDF-1 alpha-induced T lymphocyte migration and adhesion, mutant human ICAM-1 molecules were expressed in COS-7 cell line. COS-7 cells expressing ICAM-1_GFP mutant without alpha-actinin revealed no association with the actin cytoskeleton, while wild-type ICAM-showed clear association with the actin, as observed by confocal microscopy, suggesting that actinin binding motif in the cytoplasmic domain of ICAM-1 is important for the proper localization of ICAM-1 on the cell membrane. However, based on adhesion assay, we found that the cytoplasmic domain of ICAM-1 is not essential for the binding of lymphocytes which were activated by SDF-1alpha. On the other hand, ICAM-1-mediated receptor-ligand clustering event was significantly inhibited in the cells expressing ICAM-1 mutants without alpha-actinin or whole cytoplasmic domain. Taken together, these results suggest that ICAM-1 cytoplasmic domain is not essential for the adhesion but important for the ligand-receptor-mediated membrane projection of endothelial cells before trans-endothelial migration of lymphocytes.

CoPPIX Protects against TNBS Induced Colitis Through HO-1 Induction / 대한해부학회지

Crohn`s disease is a severe chronic inflammation that is treated mainly by immunosuppression, which often has serious side effects. There is a need to develop new drugs for treating this disease that have few side effects. Heme oxygenase-1 (HO-1) has immunosuppressive properties, but the mechanism of its anti-inflammatory actions is unclear. We investigated the protective effects of HO-1 on trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. An HO-1 inducer, cobalt protoporphyrin IX (CoPPIX), dramatically improved the clinical and histopathological symptoms in TNBS-induced colitis. CoPPIX suppressed tumor necrosis factor-alpha and interleukin-1beta expression and down-regulated the nuclear transcription factor kappa B activity caused by TNBS. The vehicle copper protoporphyrin IX (CuPPIX) failed to duplicate the protective effects seen with CoPPIX. Moreover, an inhibitor of HO-1 activity-zinc protoporphyrin IX-reversed the protective effects of CoPPIX on TNBS-induced colitis. In conclusion CoPPIX protects against TNBS-induced colonic damage by inducing HO-1, which might be an important target in the treatment of Crohn`s disease.