Influence of G protein-coupled receptor in macrophage activation induced by Toll-like receptor

Abstract

Macrophages play an important role in innate and adaptive immunity, and during the inflammatory process. These cell possess membrane receptors that interact with microbial structures called pattern recognition receptors (PRRs), among which the Toll-like receptors are the best studied. A feature of TLR stimulation is the activation of transcription factors, such as nuclear factor kappa B (NF-kB), the main inducer of macrophage activation. During the inflammatory response, cytokines, lipid mediators and those generated by activation of plasma system are produced, and several of these mediators act on G-protein coupled receptors. Recently, our group has shown that lipid mediator leukotriene B4 (LTB4) and its receptor BLT1 is absolutely essential to induce the expression of MyD88 adaptor protein and subsequent activation of NF-kB induced by TLRs in macrophages. The aim of this project is to study the action of different GPCRs agonists, such as platelet-activating factor (PAF), complement fragment C5a and bradykinin (BK) in the macrophage activation induced by TLRs ligands. A better understanding of the possible associations between innate immune receptors and GPCRs in macrophages may provide new therapeutic perspectives in controlling inflammatory diseases.