Dr Lakshmi Narasaiah » Публикация
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Опубликовано
2015-01-15
Опубликовано на SciPeople2015-06-29 16:48:31
ЖурналE XPERIMENTALCELLRESEARCH
Serine proteaseinhibitorsinteractwithIFN-γ through up-regulationofFasR;anoveltherapeuticstrategy against cancer
Аннотация
Among the many immunomodulatory and anti-tumor activities,IFN-γ up-regulates tumor cell death
mediated by Fasreceptor(FasR). Our and several other studies have demonstrated the involvement of
trypsin-likeproteases(TLPs)in the mode of action of IFN-γ. In the present study,we tried to unravel
the role of serine proteases in IFN-γ induced Fas-mediated cell death.Our present results show that
bothtosyl-L-Lysinechloromethylketone (TLCK) ,atrypsin like protease inhibitor and tosyl-L-phenyla-
laninechloromethylketone(TPCK) – a chymotrypsinlikeprotease(CLP)inhibitor,sensitizeHeLacellsto
Fas-mediatedcelldeath.Thecombinedeffectoftheseproteaseinhibitors with anti-Fas was stronger
than additive. Incontrast, elastaseinhibitorIII(EI) ,which also contains thechloromethyl ketone
moiety, was not active.Furthermore,co-addition ofTLCK or TPCK with IFN-γ markedlyenhanced Fas-
induced cell death. IFN-γ ledtoup-regulation of Fas R on itsown, which was further enhanced by the
co-addition of TLCKorTPCK. This was evident both by increased expression of Fas receptor on cell
surface and by
elevated FasmRNAlevel. This study may provide the basis for the design of anovel
combinatory therapeutic strategy that could enhance the eradication of tumors.