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.

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 ].…”

Evaluation of Transcriptomic Responses in Livers of Mice Exposed to the Short-Chain PFAS Compound HFPO-DA

“…The complement and coagulation cascades are part of the innate immune system and are made up of small proteins synthesized by the liver and secreted into the bloodstream ( Janeway et al, 2001 ). Unlike the adaptive immune system, which develops immunological memory using antibodies after an initial exposure to a specific pathogen, the innate immune system uses phagocytes and inflammatory signaling (e.g., cytokines and chemokines) to resolve a pathological insult ( Grabacka et al, 2021 ). PPARα has an important and specific function within the innate immune system and acts predominantly through suppression of various inflammatory reactions.…”

“…Endogenous and pharmacological PPARα agonists have been investigated for their potential therapeutic applications in several chronic inflammatory disorders (e.g., rheumatoid arthritis). The critical immunomodulatory role of PPARα has been recently reviewed by Grabacka et al (2021) .…”

PPARs as Key Mediators in the Regulation of Metabolism and Inflammation

“…Since the first observations in 1996 linking PPARα to the control of inflammation [13], the anti-inflammatory role of this receptor has been very well documented. In their review, Grabacka et al [14] discussed the interplay of PPARα with different pathways in inflammation, transcription, pattern-recognition receptor signaling, and the endocannabinoid system.…”

“…PPARs are involved in mycobacterial and viral infections. Grabacka et al [14] summarized PPARα-specific immunomodulatory functions during infections by parasites, bacteria, and viruses, as well as the modulation of processes associated with innate immunity. Tanigawa et al [29] discussed the advancement in understanding PPARs in host-mycobacteria crosstalk via their impact on the host-dependent mechanisms of lipid metabolism, anti-inflammatory processes, and autophagy during infection.…”