Peripheral Blood Mononuclear Cell Culture Supernatant Increase Fas Expression in human Proximal Tubular Cell After the Initiation of Hemodialysis in Chronic Renal Failure Patients

Jo, Sang Kyung; Yoon, Jong Woo; Cha, Dae Ryong; Cho, Won Yong; Kim, Hyung Kyu; Chang, Kyung Hyun

Abstract

Residual renal function rapidly declines after the initiation of hemodialysis and its mechanisms are supposed to be associated with frequent hypotensive episodes during hemodialysis and subsequent ischemic injury to remnant nephron, but blood-membrane interaction might play an important role because of its ability to activate complement system and other various humoral and cellular mechanisms. Blood monocytes are activated by complements, bacterial contaminants and activated monocytes are known to secrete multiple proinflammatory cytokines such as TNF-alpha, IL-1 beta. The expression of TNF-alpha and IL-1 beta in mRNA and protein level were examined by RT-PCR and ELISA respectively in patients with ESRD after the initiation of hemodialysis. Author also investigated the mRNA expression of Fas in human proximal tubular cell culture in the presence of TNF-alpha and PBMC culture supernatant before and after the initiation of hemodialysis. Compared to PBMC separated before the initiation of HD, the amount of cytokine mRNA from PBMC separated after the initiation of HD showed increased tendency from 0.97+/-0.2 to 1.12+/-0.28 for TNF-alpha(p=0.29), from 1.03+/-0.18 to 1.10+/-027 for IL-1 beta (p=0.54). TNF-alpha and IL-l beta protein level in PBMC culture supernatant also showed increased tendency from 2.25+/-0.5 to 4.254+/-3.77 for TNF-alpha (p=0.10), from 3.5+/-2.08 to 4.0+/-4.3 for IL-1 beta(p=0,25). TNF-alpha increased Fas mRNA expression dose-dependently compared to control but it was not statistically significant(p=0,37, 0.22). Compared to the the level of Fas expression in HPTC cultured in the presence of pre HD PBMC supernatant, the level of Fas expression increased significantly in the presence of post HD PBMC supernatant (0.64+/- 057 vs 1.05+/- 0.12, p=0.01). As a conclusion, cytokine gene expression and secretion can increase as a result of blood-membrane interaction and these might have some influence on the loss of residual renal function in CRF patients maintained on hemodialysis.