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    Investigação da proteína anti-inflamatória anexina a1 em culturas de explantes de vilos placentários humanos infectados por toxoplasma gondii
    (Universidade Federal de São Paulo (UNIFESP), 2016-01-29) Oliveira, Marystela Favero de [UNIFESP]; Oliani, Sonia Maria Oliani [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Introduction: Inplacental developmenttheinvasive processes, differentiation and adaptationthat occurin the bodyare intense.Some complicationsare related toinadequate developmentof the placenta, such as increased expression ofTh2 cytokineswhich can causeincreased susceptibilityto toxoplasmosis and consequently, placentaland fetalinfection.Several investigationsindicate that among theanti-inflammatory actions of the proteinannexinA1(ANXA1) isthe reduction ofcytokinelevels. This proteinhas also been linkedwithproliferativeandapoptotic processes, andstudies indicatethat their actionsmay be mediatedbyreceptors such asformylatedpeptides (FPR). Although theanti-inflammatory effects of ANXA1and its Ac2-26peptidehave beenexplored inseveral investigations, their activitiesduringplacental developmentare not yet fullyclarified.Aims- ANXA1 was evaluated in this studyin culture explants of humanplacentalvillous in thirdtrimester of pregnancy, infected or notwithToxoplasmagondii. Additionally,post-infected explants weretreated with theAc2-26peptide. Methods ?The explantswere cultured insupplementedRPMI, incubated at37oC in5% CO2 incubatorand afterwands, either infectedor not withT.gondiiRH strain. After 48 hoursof infection, samples were treated with theAc2-26peptide for 24 hours,fixed, embedded in paraffinandhistologically examined. Placentalvillousfromexplants were analyzed for immunohistochemicalto verify the expressions of ANXA1, formyl peptide receptors (FPR1 and FPR2) and COX-2 in placentas infected or not with T. gondii.Placentas from third trimester were treated with peptide Ac2-26.Gene expression of ANXA1 was also evaluated in treated samples by real time PCR.Theparasitism rate by?-galactosidase colorimetric assayand the levels ofPGE2by ELISA was detected.Results-Expressions ofANXA1protein are coincident with the FPR1receptorin trophoblasticofcontrol andinfectedgroups.After Ac2-26peptidetreatment,the intracellular parasites decrease and ANXA1 expression increase insyncytiotrophoblast cells. The expression ofCOX-2andPGE2 levelswere lower in the infected group compared with respective uninfected group without treatment. Conclusion -Together, our data highlight that Ac2-26 peptide is able to induce an anti-parasitic effect in placental explants of the advanced gestational age.In this context, the major indication isthat FPR1 receptor, COX-2 and PGE2 levels may be involved in thecontrol mechanism of T. gondiiinfections