Old Receptor, New Tricks—The Ever-Expanding Universe of Aryl Hydrocarbon Receptor Functions. Report from the 4th AHR Meeting, 29–31 August 2018 in Paris, France

Esser, Charlotte; Lawrence, B. Paige; Sherr, David H.; Perdew, Gary H.; Puga, Alvaro; Barouki, Robert; Coumoul, Xavier

doi:10.3390/ijms19113603

Cited by 46 publications

(36 citation statements)

References 27 publications

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“…Noteworthily, KYNA, apart from its influence on GPR35, is a ligand of the aryl hydrocarbon receptor (AhR). It was reported that the diet rich in AhR ligands links to the expression of genes responsible for enterocyte differentiation, the turnover rate and epithelial cells lineage fate 32 . AhR may also be implicated in the occurrence of obesity/adiposity, although currently available data are ambiguous 32 .…”

Section: Discussionmentioning

confidence: 99%

Kynurenic acid as the neglected ingredient of commercial baby formulas

Milart

Paluszkiewicz

Dobrowolski

et al. 2019

Sci Rep

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The global increase in resorting to artificial nutritional formulas replacing breastfeeding has been identified among the complex causes of the obesity epidemic in infants and children. One of the factors recently recognized to influence metabolism and weight gain is kynurenic acid (KYNA), an agonist of G protein-coupled receptor (GPR35). Therefore the aim of the study was to determine the concentration of KYNA in artificial nutritional formulas in comparison with its level in human breast milk and to evaluate developmental changes in rats exposed to KYNA enriched diet during the time of breastfeeding. KYNA levels were measured in milk samples from 25 heathy breast-feeding women during the first six months after labor and were compared with 21 time-adjusted nutritional formulas. Animal experiments were performed on male Wistar rats. KYNA was administered in drinking water. The content of KYNA in human milk increases more than 13 times during the time of breastfeeding while its level is significantly lower in artificial formulas. KYNA was detected in breast milk of rats and it was found that the supplementation of rat maternal diet with KYNA in drinking water results in its increase in maternal milk. By means of the immunoblotting technique, GPR35 was evidenced in the mucosa of the jejunum of 1-day-old rats and distinct morphological changes in the jejunum of 21-day-old rats fed by mothers exposed to water supplemented with KYNA were found. A significant reduction of body weight gain of rats postnatally exposed to KYNA supplementation without changes in total body surface and bone mineral density was observed. The rat offspring fed with breast milk with artificially enhanced KYNA content demonstrated a lower mass gain during the first 21 days of life, which indicates that KYNA may act as an anti-obesogen. Further studies are, therefore, warranted to investigate the mechanisms regulating KYNA secretion via breast milk, as well as the influence of breast milk KYNA on mass gain. In the context of lifelong obesity observed worldwide in children fed artificially, our results imply that insufficient amount of KYNA in baby formulas could be considered as one of the factors associated with increased mass gain.

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Section: Discussionmentioning

confidence: 99%

Kynurenic acid as the neglected ingredient of commercial baby formulas

Milart

Paluszkiewicz

Dobrowolski

et al. 2019

Sci Rep

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“…After ligand binding, AhR is translocated to the nucleus and mediates numerous biological effects by inducing the transcription of several genes. The AhR target genes encode drug-metabolizing enzymes such as cytochrome P450 (CYP) 1A1, 1A2, and 1B1 as well as proteins that control cell division, apoptosis, and cell differentiation (Esser et al, 2018) ( Figure 1 ).…”

Section: Skin Aging and Oxidative Stressmentioning

confidence: 99%

“…Some examples of its tasks are autoimmunity, metabolic imbalance, inflammatory skin diseases, gastrointestinal diseases, cancer development, and perhaps aging. Accurate knowledge of AhR signaling can generate novel therapies (Esser et al, 2018).…”

Section: Skin Aging and Oxidative Stressmentioning

confidence: 99%

“…Exposure of the skin to PM induces lipid peroxidation, ROS, DNA damage, apoptosis, and extracellular matrix damage (Magnani et al, 2016; Lee et al, 2016a; Zhang et al, 2017a; Idowu et al, 2019). PM binds to AhR and induces the intranuclear signaling pathway, favoring ROS formation and proinflammatory gene expression (Esser et al, 2018) (see the section The Aryl Hydrocarbon Receptor (AhR) in Skin Aging).…”

Section: Skin Aging and Air Pollutionmentioning

confidence: 99%

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Environmental Stressors on Skin Aging. Mechanistic Insights

et al. 2019

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The skin is the main barrier that protects us against environmental stressors (physical, chemical, and biological). These stressors, combined with internal factors, are responsible for cutaneous aging. Furthermore, they negatively affect the skin and increase the risk of cutaneous diseases, particularly skin cancer. This review addresses the impact of environmental stressors on skin aging, especially those related to general and specific external factors (lifestyle, occupation, pollutants, and light exposure). More specifically, we have evaluated ambient air pollution, household air pollutants from non-combustion sources, and exposure to light (ultraviolet radiation and blue and red light). We approach the molecular pathways involved in skin aging and pathology as a result of exposure to these external environmental stressors. Finally, we reflect on how components of environmental stress can interact with ultraviolet radiation to cause cell damage and the critical importance of knowing the mechanisms to develop new therapies to maintain the skin without damage in old age and to repair its diseases.

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“… higher yeast counts have been found to correlate with SD symptom and/or severity; M furfur (formerly known as Pityrosporum orbiculare , P ovale , P furfur ) has been implicated as the most common source of dandruff; Malassezia was shown to activate the NLRP3 inflammasome via the dectin‐1 and Syk signalling cascade, causing the release of the proinflammatory cytokine IL‐1β, and altered host cytokine expression profile; of the diverse chemical entities that are effective in treating SD and dandruff—such as azoles, hydroxypyridones, allylamines, selenium and zinc pyrithione—the main shared mechanism of action is their antifungal activity; Malassezia utilizes human sebum triglycerides as food, and the metabolites such as oleic acid and arachidonic acid cause aberrant epidermal differentiation, barrier defects, and inflammatory response; Malassezia infection has also been reported in domestic animals such as goats, cats and dogs as well as monkeys, associated with seborrhoea (dry or greasy) and dermatitis, suggesting that mammalian skin shares an evolutionarily conserved hyperresponsiveness to this yeast; Malassezia can produce metabolites such as indirubin and indolo[3,2‐b]carbazole that stimulate the aryl hydrocarbon receptor and can thereby modulate antigen presenting cell functions, at least in vitro . Given that aryl hydrocarbon receptor‐mediated signalling is increasingly appreciated as a major player in human skin physiology and pathology that modulates, for example skin responses to environmental toxins and bacterial stimuli, this potential pathway through which the yeast might impact on skin inflammation deserves more systemic dissection. …”

Section: Sd Aetiology: Malassezia Yeast—cause or Associated Factor?mentioning

confidence: 99%

Seborrheic dermatitis—Looking beyond Malassezia

Wikramanayake

Borda

Miteva

et al. 2019

Experimental Dermatology

101

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Seborrhoeic Dermatitis (SD) is a very common chronic and/or relapsing inflammatory skin disorder whose pathophysiology remains poorly understood. Yeast of the genus Malassezia has long been regarded as a main predisposing factor, even though causal relationship has not been firmly established. Additional predisposing factors have been described, including sebaceous activity, host immunity (especially HIV infection), epidermal barrier integrity, skin microbiota, endocrine and neurologic factors, and environmental influences. Genetic studies in humans and mouse models—with particularly interesting insights from examining the Mpzl3 knockout mice and their SD‐like skin phenotype, and patients carrying a ZNF750 mutation—highlight defects in host immunity, epidermal barrier and sebaceous activity. After synthesizing key evidence from the literature, we propose that intrinsic host factors, such as changes in the amount or composition of sebum and/or defective epidermal barrier, rather than Malassezia, may form the basis of SD pathobiology. We argue that these intrinsic changes provide favourable conditions for the commensal Malassezia to over‐colonize and elicit host inflammatory response. Aberrant host immune activity or failure to clear skin microbes may bypass the initial epidermal or sebaceous abnormalities. We delineate specific future clinical investigations, complemented by studies in suitable SD animal models, that dissect the roles of different epidermal compartments and immune components as well as their crosstalk and interactions with the skin microbiota during the process of SD. This research perspective beyond the conventional Malassezia‐centric view of SD pathogenesis is expected to enable the development of better therapeutic interventions for the management of recurrent SD.

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Old Receptor, New Tricks—The Ever-Expanding Universe of Aryl Hydrocarbon Receptor Functions. Report from the 4th AHR Meeting, 29–31 August 2018 in Paris, France

Cited by 46 publications

References 27 publications

Kynurenic acid as the neglected ingredient of commercial baby formulas

Kynurenic acid as the neglected ingredient of commercial baby formulas

Environmental Stressors on Skin Aging. Mechanistic Insights

Seborrheic dermatitis—Looking beyond Malassezia

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