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Eur J Immunol ; 46(8): 1854-66, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27198486

RESUMO

Apolipoproteins L (ApoLs) are Bcl-2-like proteins expressed under inflammatory conditions in myeloid and endothelial cells. We found that Toll-like receptor (TLR) stimuli, particularly the viral mimetic polyinosinic:polycytidylic acid (poly(I:C)), specifically induce ApoLs7/11 subfamilies in murine CD8α(+)  dendritic cells (DCs). This induction requires the TLR3/TRIF (where TRIF is TIR domain containing adapter-inducing interferon ß) signaling pathway and is dependent on IFN-ß in all ApoLs subfamilies except for ApoL7c. Poly(I:C) treatment of DCs is also associated with induction of both cell death and autophagy. ApoLs expression is related to promotion of DC death by poly(I:C), as ApoLs7/11 knockdown increases DC survival and ApoLs7 are associated with the anti-apoptotic protein Bcl-xL (where Bcl-xL is B-cell lymphoma extra large). Similarly, in human monocyte-derived DCs poly(I:C) induces both cell death and the expression of ApoLs, principally ApoL3. Finally, the BH3-like peptide of ApoLs appears to be involved in the DC death-promoting activity. We would like to propose that ApoLs are involved in cell death linked to activation of DCs by viral stimuli.


Assuntos
Apolipoproteínas/imunologia , Apoptose , Células Dendríticas/citologia , Transdução de Sinais , Receptor 3 Toll-Like/metabolismo , Proteínas Adaptadoras de Transporte Vesicular/genética , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Animais , Antígenos CD8/metabolismo , Linhagem Celular , Células Cultivadas , Células Dendríticas/metabolismo , Humanos , Interferon beta/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Poli I-C/farmacologia , Isoformas de Proteínas/imunologia , Proteína bcl-X/metabolismo
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