Signaling molecules involved in IFN-gamma-inducible nitric oxide synthase expression in the mouse trophoblast.
OBJECTIVE
We have previously shown that trophoblast can generate nitric oxide (NO) and express inducible isoform of nitric oxide synthase (iNOS). Moreover, this production was changed by the presence of interferon-gamma (IFN-gamma) establishing a relationship between trophoblast inductive response and this proinflammatory cytokine.


METHODS
As the intracellular signal transduction pathway used by IFN-gamma in target cells is the Janus kinase (JAK)-signal transducer and transcription activator (STAT), here we analyzed in the mouse trophoblast the effect of IFN-gamma and staurosporine on mRNA and protein expressions of IFN-gamma signaling molecules correlating them with iNOS expression.


RESULTS
Interferon-gamma induced iNOS expression and upregulated Jaks and Stat1, but not Stat2 transcriptions. The protein distribution matched the mRNA expression pattern. These effects were abrogated when IFN-gamma receptor was blocked by staurosporine.


CONCLUSIONS
Due to the biological effects of NO-iNOS generated on induction of apoptosis and inflammatory responses, interaction between iNOS expression and IFN-gamma-mediated signaling is very important for understanding the physiology of trophoblast at the maternal-fetal interface. Our data indicate IFN-gamma acts specifically on trophoblast, regulating the expression of signaling molecules and is fundamental for iNOS expression.
Leanza
Eduardo Cava
EC
Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Hoshida
Mara Sandra
MS
Costa
Adriana Fraga
AF
Fernandes
Cristina Maria
CM
de Fatima Pereira Teixeira
Catarina
C
Bevilacqua
Estela
E
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D005260:Female; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000494:pharmacology*; D053612:Janus Kinases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D050795:STAT2 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D019311:Staurosporine / Q000494:pharmacology; D014327:Trophoblasts / Q000201:enzymology* / Q000378:metabolism
D012333:RNA, Messenger; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II; D053612:Janus Kinases; D019311:Staurosporine