Self-regulation of the inflammatory response by peroxisome proliferator-activated receptors

Korbecki, Jan; Bobiński, Rafał; Dutka, Mieczysław

doi:10.1007/s00011-019-01231-1

Cited by 264 publications

(195 citation statements)

References 229 publications

(245 reference statements)

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“…Besides, prostacyclin and 15-HETE can activate PPARβ/δ [38]. However, 5(S)-HETE, 8(S)-HETE, 15-HETE, and LTB4 are weaker activators [94]. It is worth noting that the functioning of NK cells, which play a key role in limiting allergic inflammation in asthma, is regulated by eicosanoids including PGD2 and PGE2.…”

Section: Natural and Synthetic Ligands Of Ppars In Asthma Therapymentioning

confidence: 99%

“…The production of PGE2 and PGD2 is known to increase in the inflammation; they are transformed into antiinflammatory PGA2 and 15d-PGJ2 [94]. Besides, the resolution of acute inflammation is the process of switching the synthesis of proinflammatory lipid mediators (PG, LT) to the formation of endogenous SPMs [110].…”

Section: Natural and Synthetic Ligands Of Ppars In Asthma Therapymentioning

confidence: 99%

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Peroxisome Proliferator-Activated Receptors as a Therapeutic Target in Asthma

et al. 2020

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The complexity of the pathogenetic mechanisms of the development of chronic inflammation in asthma determines its heterogeneity and insufficient treatment effectiveness. Nuclear transcription factors, which include peroxisome proliferatoractivated receptors, that is, PPARs, play an important role in the regulation of initiation and resolution of the inflammatory process. The ability of PPARs to modulate not only lipid homeostasis but also the activity of the inflammatory response makes them an important pathogenetic target in asthma therapy. At present, special attention is focused on natural (polyunsaturated fatty acids (PUFAs), endocannabinoids, and eicosanoids) and synthetic (fibrates, thiazolidinediones) PPAR ligands and the study of signaling mechanisms involved in the implementation of their anti-inflammatory effects in asthma. This review summarizes current views on the structure and function of PPARs, as well as their participation in the pathogenesis of chronic inflammation in asthma. The potential use of PPAR ligands as therapeutic agents for treating asthma is under discussion.

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Section: Natural and Synthetic Ligands Of Ppars In Asthma Therapymentioning

confidence: 99%

Section: Natural and Synthetic Ligands Of Ppars In Asthma Therapymentioning

confidence: 99%

Peroxisome Proliferator-Activated Receptors as a Therapeutic Target in Asthma

et al. 2020

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“…PPARγ has a known role in lipid droplet formation implying a role in eicosanoid synthesis with interesting implications for tuft cell regulation. Within the stroma, PPARγ activation is known to suppress mPSC activation and is a mechanism by which the inflammatory system regulates itself through suppression of Nf-κb (39,44). Further, PPARγ activation has been shown to inhibit tumor progression and metastases in mouse models of PDA (45).…”

Section: Discussionmentioning

confidence: 99%

“…Prostaglandins are known inflammatory mediators in injury formation, resolution, and tumorigenesis (38). PPARγ expression has been described in a number of immune cell populations and activation is known to suppress inflammation (39). As a model for assessing whether PGD 2 itself is able to suppress inflammatory cell activation, we treated naïve or polarized bone marrow-derived macrophages (BMMs) in vitro with PGD 2.…”

Section: Pgd 2 Restrains Disease Progression By Promoting Environmentmentioning

confidence: 99%

Tuft cells restrain pancreatic tumorigenesis through paracrine eicosanoid signaling

DelGiorno

Chung

et al. 2019

Preprint

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Despite numerous advances in our understanding of pancreatic ductal adenocarcinoma (PDA) genetics and biology, this disease is expected to become the second leading cause of cancer-related U.S. deaths within the next few years. Incomplete understanding of how it arises precludes development of early detection and interception strategies to improve therapeutic outcomes. Acinar to ductal metaplasia involving genesis of tuft cells is one early step in PDA formation, but their functional significance has remained obscure due to their rarity and a lack of methods and relevant animal models for their molecular and functional analysis. Here, we show that deletion of tuft cell master regulator Pou2f3 eliminates pancreatic tuft cells and increases fibrosis, alters immune cell activation, and accelerates disease progression. We demonstrate that tuft cell expression of the prostaglandin D 2 synthase Hpgds restrains pancreatic disease progression in early stages by inhibiting stromal activation. Analyses of human data sets are consistent with mouse studies. We propose that tuft cells and, by inference, the associated metaplastic lesions, play a protective role early in pancreatic tumorigenesis. Significance:We find that tuft cell formation in response to oncogenic Kras is protective and restrains tumorigenesis through local production of anti-inflammatory substances, including paracrine prostaglandin D 2 signaling to the stroma. Our findings establish tuft cells as a metaplasia-induced tumor suppressive cell type. Introduction:Chemical or mechanical injury of the pancreas results in a cell state-switching event termed acinar to ductal metaplasia (ADM) where digestive enzyme producing acinar cells dedifferentiate into proliferative ductal-like cells to restore pancreas homeostasis. This process is perturbed during neoplastic progression, where, in mouse models, initiating Kras mutations prevent tissue healing and, instead, ADM is thought to progress to pancreatic intraepithelial neoplasia (PanIN) and then pancreatic ductal adenocarcinoma (PDA). This is an example of Dvorak's thesis, which states that cancer represents the ever-healing wound (1).The profound difference between the normal healing process and the perturbed response engendered by oncogene activation raises the important question of whether key cell types that result from ADM impact cancer progression. Here, we investigate the role of tuft cells as they appear in response to oncogeneinduced metaplasia in a number of cancers of human significance including lung, stomach, intestine, and pancreas (2-6).Tuft cells are solitary chemosensory cells found throughout the hollow organs of the respiratory and digestive tracts. They are readily identified by their striking morphological features, including long, blunt microvilli, deep actin rootlets, and an extensive tubulovesicular system in the supranuclear cytoplasm (7).Their expression of taste, neuronal, and inflammatory cell signaling factors is thought to enable monitoring of intraluminal homeostasis and to achieve loc...

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“…In immune cells, PPAR-γ exerts anti-inflammatory function. 100 Several stimuli, such as LPS, TNF-α and IL-1β, activate NF-κB signalling pathway that leads to the production of proinflammatory cytokines. NRs block NF-κB signalling pathway reducing inflammatory processes.…”

Section: Nuclear Receptors and Th17 Polarization: The Role Of Ppar mentioning

confidence: 99%

Deciphering targets of Th17 cells fate: From metabolism to nuclear receptors

2019

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Evidence indicates that reprogramming of metabolism is critically important for the differentiation of CD4 + T lymphocytes, and the manipulation of metabolic pathways in these cells may shape their fate and function. Distinct subgroups from T lymphocytes, such as Th17, adopt specific metabolic programmes to support their needs. Some important metabolic reactions, such as glycolysis, oxidative phosphorylation, are considered important for the differentiation of these lymphocytes. Since their discovery nearly a decade ago, Th17 lymphocytes have received significant attention because of their role in the pathology of several immune‐mediated inflammatory diseases such as multiple sclerosis. In this review, it will be discussed as the involvement of T cell metabolism and as metabolic reprogramming in activated T cells dictates fate decisions to Th17. The involvement of nuclear receptors such as RORyt e PPARs in the induction of Th17 cells was also discussed. Understanding the metabolic pathways involved in the differentiation of the distinct subgroups of T lymphocytes helps in the design of promising therapeutic proposals.

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Self-regulation of the inflammatory response by peroxisome proliferator-activated receptors

Cited by 264 publications

References 229 publications

Peroxisome Proliferator-Activated Receptors as a Therapeutic Target in Asthma

Peroxisome Proliferator-Activated Receptors as a Therapeutic Target in Asthma

Tuft cells restrain pancreatic tumorigenesis through paracrine eicosanoid signaling

Deciphering targets of Th17 cells fate: From metabolism to nuclear receptors

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