[Effects of fosinopril and losartan on the expression of Toll- like receptor 4 in renal tubular epithelia cells].
OBJECTIVE
To determine the mechanism of Toll-like receptor 4(TLR4) in hypertensive renal injury and the protective effect of fosinopril(Fos) and losartan(Los).


METHODS
NRK-52E was incubated into 5 groups: NRK-52E (normal control), NRK-52E+AngII, NRK-52E+AngII+Fos(10(-5) mmol/L),and NRK-52E+AngII+Los(10(-5) mmol/L), NRK-52E +AngII+Fos(10(-5) mmol/L)+Los(10(-5) mmol/L). TLR4-specific RNAi plasmids were stably transfected into NRK-52E. After 24 h, TLR4, IL-6, and TNF-alpha mRNAs were examined by reverse transcription-polymerase chain reaction(RT-PCR). TLR4 proteins were detected by Western blot, NF-kappaB nuclear translocations were tested by immunocytochemistry,and IL-6 and TNF-alpha supernatant levels were tested by enzyme linked immuno-sorbent assay(ELISA).


RESULTS
TLR4, NF-kappaB, IL-6,and TNF-alpha were highly expressed in AngII induced NRK-52E(P<0.01). In NRK-52E that was stably transfected TLR4-special RNAi plamids, TLR4 protein and mRNA expression were obviously inhibited(P<0.05). After stimulation by AngII, the TLR4, IL-6, TNF-alpha levels in the stabe transfection group were increased compared with the normal group(P<0.05). Fos or/and Los down-regulated TLR4, IL-6, and TNF-alpha expressions(P<0.05), but no cooperation was observed.


CONCLUSIONS
TLR4 may lead to inflammatory reaction in hypertensive renal injury. Fos or/and Los can decrease the expressions of TLR4 and correlate inflammatory factors, which may be part of the renal protective mechanism.
Tang
Tian-feng
TF
Department of Nephrology, Xiangya Hospital, Central South University, Changsha 410008, China.
Zhou
Qiao-ling
QL
Zhu
Li-li
LL
Tang
Rong
R
Ao
Xiang
X
D000818:Animals; D002460:Cell Line; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism*; D017328:Fosinopril / Q000494:pharmacology*; D006973:Hypertension / Q000150:complications; D007674:Kidney Diseases / Q000517:prevention & control; D007684:Kidney Tubules / Q000166:cytology* / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology*; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis* / Q000235:genetics
D012333:RNA, Messenger; D051197:Toll-Like Receptor 4; D019808:Losartan; D017328:Fosinopril