The efferocytosis (phagocytosis of apoptotic cells) promotes the synthesis of anti-inflammatory mediators, such as transforming growth factor (TGF ²), prostaglandin E2 (PGE2) and interleukin-10 (IL-10), important for differentiation of regulatory T cells (Treg). However, the phagocytosis of infected apoptotic cells directs the synthesis of anti and pro-inflammatory cytokines such as TGF², IL-6 and IL-23 known to promote the induction of T helper 17 (Th17). Results obtained recently by our group showed that the phagocytosis of infected apoptotic cells with Escherichia coli by dendritic cells promotes in addition of TGF², IL-6 and IL-1², the synthesis of high levels of PGE2. Furthermore, we found that PGE2 through EP4 receptor inhibits the differentiation of Th17 lymphocytes by modulating the expression of IL-1 receptor expression by Th lymphocytes.However, the mechanism by which PGE2 via EP4 inhibits IL-1R expression in lymphocytes Th17 remains unknown. Studies suggest that activation of STAT 3 (Signal transducer and activator of transcription-3) by the IL-6 signaling is one of the major pathways involved in the expression of IL-1R and differentiation of Th17. Moreover, it has been demonstrated that PGE2 in monocytes increases the expression and activity of the STAT3 inhibitors, SOCS3 (Suppressor of cytokine signaling 3), and decreases the expression of IRF4 (Interferon Regulatory Factor 4) an important transcription factor in the differentiation of Th17. Therefore the hypothesis of this project is that PGE2 via EP4, induces expression of SOCS3, which prevents the activation of STAT3, affecting the expression of IL-1 receptor, as well as transcription factors involved in the differentiation of Th17 as IRF4 and ROR³t.
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