Crosstalk between Peroxisome Proliferator-Activated Receptors andToll-Like Receptors: A Systematic Review

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 proliferatoractivatedreceptors (PPARs) with three isoforms are transcription factors classified as a subfamilyof nuclear receptor proteins, and are of significant regulatory activity in cellular differentiation,development, metabolism, and tumorigenesis. It is well established that PPARs agonists displayanti-inflammatory effects through inhibition of the nuclear factor-kappa B (NF-κB) pathway, akey regulator of immune and inflammatory responses, in a sense that TLRs signaling pathwaysare mainly toward activation of NF-κB. Through a systematic review of previous studies, weaimed to address and clarify the reciprocal interaction between TLRs and PPARs in hope to findalternative therapeutic approaches for inflammatory diseases. Among the available scientificdatabase, 31 articles were selected for this review. A comprehensive review of this databaseconfirms the presence of a cross-talk between PPARs and TLRs, indicating that not onlyPPARs stimulation may affect the expression level of TLRs via several mechanisms leading tomodulating 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 interactionbetween PPARs and TLRs is a potential therapeutic target in disease treatment.

Keywords: Peroxisome proliferator-activated receptor, Toll-like receptor, Interaction, Crosstalk