Activation Of Aryl Hydrocarbon Receptor Pathway Research Articles

The role of aryl hydrocarbon receptor in vitiligo: a review.

Vitiligo is an acquired autoimmune dermatosis characterized by patchy skin depigmentation, causing significant psychological distress to the patients. Genetic susceptibility, environmental triggers, oxidative stress, and autoimmunity contribute to melanocyte destruction in vitiligo. Due to the diversity and complexity of pathogenesis, the combination of inhibiting melanocyte destruction and stimulating melanogenesis gives the best results in treating vitiligo. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that can regulate the expression of various downstream genes and play roles in cell differentiation, immune response, and physiological homeostasis maintenance. Recent studies suggested that AhR signaling pathway was downregulated in vitiligo. Activation of AhR pathway helps to activate antioxidant pathways, inhibit abnormal immunity response, and upregulate the melanogenesis gene, thereby protecting melanocytes from oxidative stress damage, controlling disease progression, and promoting lesion repigmentation. Here, we review the relevant literature and summarize the possible roles of the AhR signaling pathway in vitiligo pathogenesis and treatment, to further understand the links between the AhR and vitiligo, and provide new potential therapeutic strategies.

LMP2A suppresses the role of AHR pathway through ERK signal pathway in EBV-associated gastric cancer

ObjectiveTo investigate the function of the aryl hydrocarbon receptor (AHR) pathway in Epstein-Barr Virus (EBV)-associated gastric cancer (EBVaGC) and to explore the relationship between EBV and AHR expression. MethodsThe expression of AHR in EBVaGC and EBV negative GC (EBVnGC) tissues was detected by immunohistochemistry (IHC). Real-time qPCR (RT-qPCR) and Western blot analysis were used to examine the expression of AHR, cytochrome P450 1A1 (CYP1A1), and cytochrome P450 1B1 (CYP1B1) in gastric cancer cells. The cell proliferation and migration assay were tested by CCK8 and transwell analysis. EBV-encoded latent membrane protein 2A (LMP2A) was over-expressed in SGC7901 cells and silenced in AGS-EBV cells to further identify its role in EBV positive GC cells. ResultsIt was found that EBV infection inhibited the expression of AHR in gastric cancer tissues and cell lines. We also found that the activation of AHR pathway can promote cell proliferation and migration. However, the function was restricted in EBVaGC cell lines compared with EBVnGC. LMP2A can suppress AHR expression and pathway activation by activating phosphorylation of extracellular signal-regulated kinase (ERK) in EBV positive GC cell lines. ConclusionEBV-encoded LMP2A regulated the function of the AHR pathway by activating the ERK signal pathway in EBV positive GC cell lines.

Detrimental activation of AhR pathway in cancer: an overview of therapeutic strategies

Sustained transcriptional activation of the aryl hydrocarbon receptor (AhR) promotes tumour growth and impairs the immune defence, at least for cutaneous melanoma and glioma. AhR ligands are produced by the tumour microenvironment (TME) and by the tumour itself (intracrine). The recent identification of interleukin-4-induced-1 (IL4I1), a parallel pathway to indoleamine 2 3-dioxygenase 1 (IDO1)/ tryptophan 2,3-dioxygenase (TDO), and its ability to generate AhR ligands, confirms that a complete inhibition of AhR ligand production might be difficult to reach. Here, we have focused on recent discoveries explaining the large varieties of AhR ligands and the functional consequences in terms of cancer cell plasticity and consecutive therapy resistance. We also examined therapeutic strategies targeting the AhR signalling pathway and their possible adverse effects. Since the end of 2019, two phase I clinical trials have investigated the ability of the AhR antagonist to 'reset' the immune system and re-sensitize the cancer cells to therapies by preventing their dedifferentiation.

Lactobacillus bulgaricus OLL1181 activates the aryl hydrocarbon receptor pathway and inhibits colitis

Increasing evidence suggests that the aryl hydrocarbon receptor (AhR) pathway has an important role in the regulation of inflammatory responses. Most recently, we have shown that the activation of the AhR pathway by a potent AhR agonist inhibits the development of dextran sodium sulfate (DSS)-induced colitis, a model of human ulcerative colitis, by the induction of prostaglandin E2 (PGE2) in the large intestine. Because several strains of probiotic lactic acid bacteria have been reported to inhibit DSS-induced colitis by unidentified mechanisms, we hypothesized that particular strains of lactic acid bacterium might have the potential to activate the AhR pathway, thereby inhibiting DSS-induced colitis. This study investigated whether there are specific lactic acid bacterial strains that can activate the AhR pathway, and if so, whether this AhR-activating potential is associated with suppression of DSS-induced colitis. By using AhR signaling reporter cells, we found that Lactobacillus bulgaricus OLL1181 had the potential to activate the AhR pathway. OLL1181 also induced the mRNA expression of cytochrome P450 family 1A1 (CYP1A1), a target gene of the AhR pathway, in human colon cells, which was inhibited by the addition of an AhR antagonist, α-naphthoflavon (αNF). In addition, mice treated orally with OLL1181 showed an increase in CYP1A1 mRNA expression in the large intestine and amelioration of DSS-induced colitis. Thus, OLL1181 can induce activation of the intestinal AhR pathway and inhibit DSS-induced colitis in mice. This strain of lactic acid bacterium has therefore the potential to activate the AhR pathway, which may be able to suppress colitis.