Effects of Mixed Leukocyte Reaction, Hydrocortisone, or Cyclosporine A on Expression of Adhesion Molecules by Endothelial and Mesangial cells / 대한내과학회지

ABSTRACT

OBJECTIVES: ICAM-1, VCAM-1, and betal integrins mediate cell-cell or cell-matrix interactions. We investigated effects of mixed leukocyte reaction (MLR), cyclosporine A (CsA), or hydrocortisone (HC) on their expression by endothelial (EnC) and mesangial cells (MC). METHODS: MLR was performed with or without CsA or HC for 5 days. After adding 25N MLR supernatant, cytokines or CsA to MC or EnC, the expression of VCAM-1, ICAM-1, and alpha3beta1 and a501 integrins was examined by using cell surface enzyme immunoassays or flow cytometry. RESULTS: MLR supernatant induced a marked increase in the expression of ICAM-1 and VCAM-1 on MC or EnC(p<0.001). HC treatment during MLR effectively inhibited MLR-induced upregulation of VCAM-1 and ICAM-1 on both cells (p<0.005). HC had, however, no inhibitory effect on VCAM-1 expression when added with MLR supernatant to cells. CsA treatment during MLR caused a modest decrease in MLR-induced expression of VCAM-1 on EnC, but had no effect on that of ICAM-1. INFgamma or TGFbeta1 stimulated expression of VCAM-1, and INFgamma, IL-1beta, or TNF alpha expression of ICAM-1 on MC after 24 hr. INFgamma, or TGFbeta1 enhanced expression of alpha3beta1 or alpha5beta1 integrins on MC after 5 days. CsA caused a modest decrease in basal expression of VCAM-1, and also decreased the basal, or INFgamma, or TGFbeta1-induced expression of alpha3beta1 and alpha5beta1 integrins on MC. CONCLUSION: Alloreactive lymphocytes and monocytes upregulate expression of VCAM-1 and ICAM-1 on EnC and MC maybe by secretion of cytokines such as INFgamma, and facilitate leukocytes attachment and following renal or vascular injury. HC effectively prevent the upregulation of VCAM-1 and ICAM-1 by inhibiting the release of cytokines during MLR. CsA did not cause an increase in the expression of VCAM-1 and beta1 integrin.