Crosstalk between Peroxisome Proliferator-Activated Receptors and Toll-Like Receptors: A Systematic Review.

Nasim Dana,Shaghayegh Haghjooy-Javanmard,Golnaz Vaseghi

doi:10.15171/apb.2019.003

Nasim Dana, Shaghayegh Haghjooy-Javanmard + Show 1 more

Open Access

https://doi.org/10.15171/apb.2019.003

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Abstract

As one of the four major families of pattern recognition receptors (PRRs), toll like receptors (TLRs) are crucial and important components of the innate immune system. Peroxisome proliferatoractivated receptors (PPARs) with three isoforms are transcription factors classified as a subfamily of nuclear receptor proteins, and are of significant regulatory activity in cellular differentiation, development, metabolism, and tumorigenesis. It is well established that PPARs agonists display anti-inflammatory effects through inhibition of the nuclear factor-kappa B (NF-κB) pathway, a key regulator of immune and inflammatory responses, in a sense that TLRs signaling pathways are mainly toward activation of NF-κB. Through a systematic review of previous studies, we aimed to address and clarify the reciprocal interaction between TLRs and PPARs in hope to find alternative therapeutic approaches for inflammatory diseases. Among the available scientific database, 31 articles were selected for this review. A comprehensive review of this database confirms the presence of a cross-talk between PPARs and TLRs, indicating that not only PPARs stimulation may affect the expression level of TLRs via several mechanisms leading to modulating TLRs activities, but also TLRs have the potential to moderate the expression of PPARs. We, therefore, conclude that, as a key regulator of the innate immune system, the interaction between PPARs and TLRs is a potential therapeutic target in disease treatment.

Highlights

Toll-like receptors (TLRs) are a family of immune system glycoproteins with 13 members, 10 of which have been identified in human, and are responsible for several activities.[1]
They reported that treatment with TGZ inhibited toll like receptors (TLRs)-induced DC activation through inhibiting of NF-κB and mitogen-activated protein (MAP) kinase pathways, two important regulation mechanisms of TLR and Peroxisome proliferatoractivated receptors (PPARs) γ– mediated signaling in DCs.[13]
They showed that exposure to LPS moderated PPARγ messenger RNA (mRNA) synthesis in macrophages did not change the PPARγ expression level in TLR-4knockout mice macrophages but attenuated the PPARγ expression in functional TLR-4-reconstructed cells

Summary

Introduction

Toll-like receptors (TLRs) are a family of immune system glycoproteins with 13 members, 10 of which have been identified in human, and are responsible for several activities.[1]. B (NF-κB ) and activator protein-1 (AP-1).[6] Various inflammatory stimuli can activate NF-κB in different diseases and induce transcription of proinflammatory cytokines, chemokines, adhesion molecules and matrix metalloproteinases (MMPs).[7] Another class of transcription factors involved in modulating the inflammation responses is peroxisome proliferator-activated receptors (PPARs), a subfamily of nuclear receptor proteins with three members: I) α (alpha), expressed in liver, kidney, heart, muscle, adipose tissue, and others, II) β/δ (beta/delta), expressed in many tissues but markedly in brain, adipose tissue, and skin, and III) γ (gamma) expressed in virtually all tissues.[8] By inactivation of p65 complexes or through inducing IκBα (as the main inhibitor of NF-κB signaling pathway), PPARs can directly attenuate the expression of inflammatory responses genes. Since many of anti-inflammatory genes are regulated by NF-κB and AP-1 pathways, PPARs agonist may have potential regulatory application in a wide range of inflammatory disorders.[9]

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