Direct contact between human peripheral blood mononuclear cells and renal fibroblasts facilitates the expression of monocyte chemoattractant protein-1.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Hao
Lirong
L
Department of Nephrology, Saitama Medical School, Irumagun, Saitama, Japan.
Okada
Hirokazu
H
Kanno
Yoshihiko
Y
Inoue
Tsutomu
T
Kobayashi
Tatsuya
T
Watanabe
Yusuke
Y
Strutz
Frank
F
Müller
Gerhard A
GA
Suzuki
Hiromichi
H
D000906:Antibodies / Q000494:pharmacology; D002450:Cell Communication; D002460:Cell Line; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D018920:Coculture Techniques; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D007668:Kidney / Q000166:cytology*; D007963:Leukocytes, Mononuclear / Q000166:cytology*; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology
D000906:Antibodies; D018932:Chemokine CCL2; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1