The Role of PPAR Alpha in the Modulation of Innate Immunity

Abstract

Peroxisome proliferator-activated receptor α is a potent regulator of systemic and cellular metabolism and energy homeostasis, but it also suppresses various inflammatory reactions. In this review, we focus on its role in the regulation of innate immunity; in particular, we discuss the PPARα interplay with inflammatory transcription factor signaling, pattern-recognition receptor signaling, and the endocannabinoid system. We also present examples of the PPARα-specific immunomodulatory functions during parasitic, bacterial, and viral infections, as well as approach several issues associated with innate immunity processes, such as the production of reactive nitrogen and oxygen species, phagocytosis, and the effector functions of macrophages, innate lymphoid cells, and mast cells. The described phenomena encourage the application of endogenous and pharmacological PPARα agonists to alleviate the disorders of immunological background and the development of new solutions that engage PPARα activation or suppression.

Heme in Bacterial Pathogenesis and as an Antimicrobial Target

“…Conjugated bilirubin is an agonist of peroxisome proliferator-activated receptor alpha (PPARα), , which is a known receptor in the gastrointestinal tract to drive immune response in vertebrates. , Taken together, these findings underscore how heme and its degradation catabolites play various roles in shaping vertebrate immune responses.…”

Heme in Bacterial Pathogenesis and as an Antimicrobial Target

“…Conjugated bilirubin is an agonist of peroxisome proliferator-activated receptor alpha (PPARα), , which is a known receptor in the gastrointestinal tract to drive immune response in vertebrates. , Taken together, these findings underscore how heme and its degradation catabolites play various roles in shaping vertebrate immune responses.…”

N-Palmitoyl-D-Glucosamine Inhibits TLR-4/NLRP3 and Improves DNBS-Induced Colon Inflammation through a PPAR-α-Dependent Mechanism

“…The sequel of events triggered by TLR-4 activation, including NF-kB and NLRP3 activation, and the release of IL-1β, IL-6, and TNF-α, are considered the most involved in persistent intestinal inflammation triggering and maintenance during colitis [8,14], and HIV-1 Tat-induced diarrhea [33]. In this context, PPAR-α agonists, such as PEA, may mediate TLR-4 down-regulation and efficiently suppress the inflammatory process similar to the evidence observed in vitro [15], clinical studies [34], endotoxin induced-uveitis rat model, and DSS-induced colitis mice model [21,35].…”

In situ self-assembled stimulus-responsive and conductive hydrogel modulate myocardial infarction inflammatory homeostasis via PPARα/NFκB signaling and enhance the therapeutic efficacy of hiPSC-CMs

“…The NFκB pathway plays an important role in the innate immune response mediated by various diseases, and when stimulated, a series of cascade reactions occur and induce the expression of inflammatory factors (e.g., TNF-α, IL-1β, and IL-6), which can further lead to tissue damage [ 50 ]. PPARα exerts anti-inflammatory effects [ 51 ], and it is a transcriptional inhibitor of NFκB in adipocytes, which inhibits the production of inflammatory cytokines and regulates innate and adaptive immunity in part through negative regulation of NFκB [ 52 ]. NFκB signaling is a major regulator of macrophage-inflammatory responses in MI and IR injury [ 53 ].…”

Heme in Bacterial Pathogenesis and as an Antimicrobial Target

“…Conjugated bilirubin is an agonist of peroxisome proliferator-activated receptor alpha (PPARα), , which is a known receptor in the gastrointestinal tract to drive immune response in vertebrates. , Taken together, these findings underscore how heme and its degradation catabolites play various roles in shaping vertebrate immune responses.…”

N-Palmitoyl-D-Glucosamine Inhibits TLR-4/NLRP3 and Improves DNBS-Induced Colon Inflammation through a PPAR-α-Dependent Mechanism

“…The sequel of events triggered by TLR-4 activation, including NF-kB and NLRP3 activation, and the release of IL-1β, IL-6, and TNF-α, are considered the most involved in persistent intestinal inflammation triggering and maintenance during colitis [8,14], and HIV-1 Tat-induced diarrhea [33]. In this context, PPAR-α agonists, such as PEA, may mediate TLR-4 down-regulation and efficiently suppress the inflammatory process similar to the evidence observed in vitro [15], clinical studies [34], endotoxin induced-uveitis rat model, and DSS-induced colitis mice model [21,35].…”

In situ self-assembled stimulus-responsive and conductive hydrogel modulate myocardial infarction inflammatory homeostasis via PPARα/NFκB signaling and enhance the therapeutic efficacy of hiPSC-CMs

“…The NFκB pathway plays an important role in the innate immune response mediated by various diseases, and when stimulated, a series of cascade reactions occur and induce the expression of inflammatory factors (e.g., TNF-α, IL-1β, and IL-6), which can further lead to tissue damage [ 50 ]. PPARα exerts anti-inflammatory effects [ 51 ], and it is a transcriptional inhibitor of NFκB in adipocytes, which inhibits the production of inflammatory cytokines and regulates innate and adaptive immunity in part through negative regulation of NFκB [ 52 ]. NFκB signaling is a major regulator of macrophage-inflammatory responses in MI and IR injury [ 53 ].…”

Heme in Bacterial Pathogenesis and as an Antimicrobial Target

“…Conjugated bilirubin is an agonist of peroxisome proliferator-activated receptor alpha (PPARα), , which is a known receptor in the gastrointestinal tract to drive immune response in vertebrates. , Taken together, these findings underscore how heme and its degradation catabolites play various roles in shaping vertebrate immune responses.…”

N-Palmitoyl-D-Glucosamine Inhibits TLR-4/NLRP3 and Improves DNBS-Induced Colon Inflammation through a PPAR-α-Dependent Mechanism

“…The sequel of events triggered by TLR-4 activation, including NF-kB and NLRP3 activation, and the release of IL-1β, IL-6, and TNF-α, are considered the most involved in persistent intestinal inflammation triggering and maintenance during colitis [8,14], and HIV-1 Tat-induced diarrhea [33]. In this context, PPAR-α agonists, such as PEA, may mediate TLR-4 down-regulation and efficiently suppress the inflammatory process similar to the evidence observed in vitro [15], clinical studies [34], endotoxin induced-uveitis rat model, and DSS-induced colitis mice model [21,35].…”

In situ self-assembled stimulus-responsive and conductive hydrogel modulate myocardial infarction inflammatory homeostasis via PPARα/NFκB signaling and enhance the therapeutic efficacy of hiPSC-CMs

“…The NFκB pathway plays an important role in the innate immune response mediated by various diseases, and when stimulated, a series of cascade reactions occur and induce the expression of inflammatory factors (e.g., TNF-α, IL-1β, and IL-6), which can further lead to tissue damage [ 50 ]. PPARα exerts anti-inflammatory effects [ 51 ], and it is a transcriptional inhibitor of NFκB in adipocytes, which inhibits the production of inflammatory cytokines and regulates innate and adaptive immunity in part through negative regulation of NFκB [ 52 ]. NFκB signaling is a major regulator of macrophage-inflammatory responses in MI and IR injury [ 53 ].…”