Hao Lirong, Okada Hirokazu, Kanno Yoshihiko, Inoue Tsutomu, Kobayashi Tatsuya, Watanabe Yusuke, Strutz Frank, Müller Gerhard A, Suzuki Hiromichi
Department of Nephrology, Saitama Medical School, Irumagun, Saitama, Japan.
Am J Nephrol. 2003 Jul-Aug;23(4):208-13. doi: 10.1159/000071480. Epub 2003 May 27.
Cell-to-cell interaction is thought to be an important feature of a variety of biological processes. As far as the proinflammatory process is concerned, the interaction between mesangial cells and monocytes/macrophages induces the expression of monocyte chemoattractant protein-1 (MCP-1), and this may play a role in glomerulonephritis. In this study, we investigated whether the cell-to-cell interaction between immune cells and renal fibroblasts induces MCP-1 gene expression, which may be involved in interstitial inflammation in the kidney.
Human renal fibroblast cell lines, tNKF (from a normal kidney) and tFKIF (from a kidney with fibrosis), and peripheral blood mononuclear cells (PBMC) were used to assess the effect of cell-to-cell contact on the expression of MCP-1 mRNA in the fibroblasts. The expression of the MCP-1 gene in the fibroblasts was also examined after stimulation with tumor necrosis factor-alpha (TNF-alpha) and the culture supernatant from PBMC. RT-PCR was used to detect MCP-1 mRNA expression. Neutralizing antibodies to intercellular adhesion molecule-1 (ICAM-1) and vascular endothelial adhesion molecule-1 (VCAM-1) were used to block the cell-to-cell contact between the fibroblasts and PBMC.
TNF-alpha and the culture supernatant from PBMC increased MCP-1 gene expression in tNKF cells. Contact culture with PBMC also significantly increased MCP-1 gene expression in tNKF cells. Although the basal level of MCP-1 mRNA was higher in tFKIF than tNKF cells, tFKIF cells did not respond significantly to any stimulation in this study. Following pretreatment with anti-ICAM-1 antibody, MCP-1 gene expression in tNKF cells was significantly suppressed in contact culture with PBMC. Anti-VCAM-1 antibody treatment had no effects.
It is suggested that the interaction between renal fibroblasts and PBMC was mediated through direct contact and by secreted humoral factors. ICAM-1 on renal fibroblasts may be involved in the direct cell-to-cell interaction inducing MCP-1 gene expression, which seems to be involved in renal interstitial inflammation.
