Mechanism of suppression of T cell AICD mediated by macrophage- and DC-derived prostaglandin 'E IND.2' (2006)
- USP affiliated authors: NEGRO, SONIA JANCAR - ICB ; RUSSO, MOMTCHILO - ICB ; MENDES, JOAO GUSTAVO PESSINI AMARANTE - ICB
- Unidade: ICB
- Assunto: IMUNOLOGIA
- Language: Inglês
- Abstract: Introduction and Aims: In a previous study, our group has shown that prostaglandin E2 (PGE2) secreted by macrophage and dendritic cells were able to inhibit T cell death induced by anti-CD3 antibodies (AICD). This inhibition was probably due to the downmodulation of FasL mRNA, as the Fas signaling pathway was entirely preserved. Methods and Results: In the present work, we show by flow cytometry that the FasL protein levels in the cell surface are also reduced and confirmed the suppression of FasL transcription by luciferase reporter assays. The mechanism of suppression of AICD and FasL by PGE2 seems to be mediated by EP2 (prostaglandin receptor subtype 2), as butaprost, a specific agonist for this receptor, mimicked the effects of PGE2. The addition of AH6809, a specific inhibitor of EP1, did not reduced PGE2 nor butaprost effects, demonstrating that EP1 stimulation is not essential.The EP2 stimulation leads to adenylate cyclase activation, cAMP upregulation, and triggering of two different pathways (PKA and EPAC activation). We used specific agonists for each pathway and demonstrated that only PKA-mediated pathway is capable of blocking AICD, although EPAC activation seems to potentiate PKA-mediated inhibition of AICD. In order to investigate which of the transcription factors important for FasL upregulation were repressed by EP2- and PKAdependent PGE2 signaling, we used luciferase reporter assays. In these assays, each plasmidconstruct was responsive to a distinct transcription factor, namely NFAT, NF-ê B, AP-1, CREB and c-Myc. Conclusions: PGE2 mediates AICD suppression inhibiting FasL transcription through EP2 receptor coupling, cAMP-dependent PKA activation, altering the balance of transcription factors important for FasL transcription.
- Título do periódico: Abstracts
- Conference titles: Meeting of the Brazilian Society for Immunology
ABNTWEINLICH, R; BASTOS, K R; CHEHAB, C F; et al. Mechanism of suppression of T cell AICD mediated by macrophage- and DC-derived prostaglandin 'E IND.2'. Anais.. São Paulo: [s.n.], 2006.
APAWeinlich, R., Bastos, K. R., Chehab, C. F., Ulbrich, A. G., Serezani, C. H., Peters-Golden, M., et al. (2006). Mechanism of suppression of T cell AICD mediated by macrophage- and DC-derived prostaglandin 'E IND.2'. In Abstracts. São Paulo.
NLMWeinlich R, Bastos KR, Chehab CF, Ulbrich AG, Serezani CH, Peters-Golden M, Jancar S, Russo M, Amarante-Mendes GP. Mechanism of suppression of T cell AICD mediated by macrophage- and DC-derived prostaglandin 'E IND.2'. Abstracts. 2006 ;
VancouverWeinlich R, Bastos KR, Chehab CF, Ulbrich AG, Serezani CH, Peters-Golden M, Jancar S, Russo M, Amarante-Mendes GP. Mechanism of suppression of T cell AICD mediated by macrophage- and DC-derived prostaglandin 'E IND.2'. Abstracts. 2006 ;
- Macrophage- and DC-derived PGE2 protects T cells from AICD by preventing FasL upregulation
- FASL upregulation and T cell death by AICD are prevented by macrophage- and DC-derived PGE2
- Cross-talk between innate and adaptive immunity: TLR4/MYD88-dependent, LPS-induced synthesis of PGE2 by macrophages or dendritic cells prevents anti-CD3- mediated apoptosis of T cells
- PGE2 derivada de macrófagos ou células dendríticas protege linfócitos T da AICD bloqueando a expressão de FasL
- A novel pathway for inducible nitric oxide synthase activation by cytosolic flagellin dependent on caspase-1
- A suggestive role of naip5 on inos activation in flagellin-stimulated macrophages
- Phagocytosis of apoptotic and necrotic cells by murine peritoneal macrophages involvement of PAF receptors
- TLR4/MYD88-dependent, LPS-induced synthesis of PGE2 by macrophages or dendritic cells prevents anti-CD3-mediated CD95L upregulation in T cells
- A suggestive role of NAIP5 on INOS activation
- Regulação do CD95L por PGE2 e seu impacto na morte de linfócitos T.
How to cite
A citação é gerada automaticamente e pode não estar totalmente de acordo com as normas