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| Author(s): |
Edson Kiyotaka Ishizuka
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) |
| Defense date: | 2016-05-18 |
| Examining board members: |
Sonia Jancar Negro;
Pedro Augusto Carlos Magno Fernandes;
Rosely Oliveira Godinho;
Alessandra Pontillo;
Nancy Starobinas
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| Advisor: | Sonia Jancar Negro; Carlos Henrique Cardoso Serezani |
| Abstract | |
Toll-like receptors (TLRs) and platelet-activating factor receptor (PAF-R) are highly expressed in macrophages. In this work, we investigated the effect of PAF-R activation on peritoneal macrophages responses to TLR agonists. We found that exogenous PAF inhibited the production of pro-inflammatory cytokines (IL-12p40, IL-6 and TNF-α) and increased IL-10 in macrophages challenged with Pam3Cys (TLR2) and LPS (TLR4), but not by Poly(I:C) (TLR3). PAF did not affect MyD88 and TRIF expression, suggesting that PAF modulation on cytokines is downstream to adaptors. PAF inhibited LPS-induced phosphorylation of NF-κB p65 that drives inflammatory cytokine gene expression and increased NF-κB p105 precursor phosphorylation, which induces IL-10 expression. These findings indicate that in LPS-activated macrophages, the impaired transcriptional activity of p65 subunit and enhanced p105 phosphorylation induced by PAF are responsible for the downregulation of pro-inflammatory cytokines and up-regulation of IL-10, respectively. (AU) | |
| FAPESP's process: | 12/07662-6 - Influence of G protein-coupled receptor in macrophage activation induced by Toll-like receptor |
| Grantee: | Edson Kiyotaka Ishizuka |
| Support Opportunities: | Scholarships in Brazil - Doctorate |