Objectives: This study was performed to observe the effects of conditioned media (CM) of cultured mononuclear cells (MNC) on the expression of beta 1 integrin and intercellular adhesion molecule(ICAM)-1 on mesangial cells and the modulation by TGF-beta, TNF alpha, or hydroxyl radical Also these were examined in anti-Thy mesangial proliferative GN (MsPGN) or puromycin aminonucleoside nephrosis(PAN).
Methods: The expression of beta 1 integrin and ICAM-1 on mesangial cells was examined by ELISA and the modulation by TGF-beta, TNF alpha, or hydroxyl radical was investigated by using neutralizing antibody and dimethylthiourea. [.OH] scavenger.
Results: The CM of MNC from Control suppressed the beta 1 integrin expression and thymidine incorporation and increased ICAM-1 expression on mesangial cells, compared to media alone. Especially the significant increase in ICAM-1 expression was reversed by anti-TNF alpha antibody. beta 1 integrin expression on mesangial cells was higher by the addition of CM of MNC in MsPGN than in Control, which was prevented by anti-TGF beta antibody or dimethylthiourea. ICAM-1 expression was not different among groups. Thymidine incorporation by adding CM of MNC was lower in MsPGN and PAN, which was mitigated by anti-TGF beta and anti-TNF alpha. Thus the ratio of the expression of ICAM-1 to thymidine incorporation was higher in MsPGN and PAN.
Conclusion: The expression of beta 1 integrin and ICAM-1, and the thymidine incorporation on mesangial cells are directly regulated by MNC, maybe through factors such as TGF beta or TNF alpha. In MsPGN, the overexpression of beta 1 integrin induced by MNC through TGF beta or hydroxyl radical on day 3 may be related to the pathogenesis.