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T lymphocyte populations within the lamina propria
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Thomas T. MacDonald, Antonio Di Sabatino
Unlike the genes that encode IL-17A and IL-17F, expression of the gene encoding IL-22 is strictly dependent on the aryl hydrocarbon receptor, a ligand-activated transcription factor that binds a wide array of environmental and endogenous aromatic hydrocarbons, including tryptophan metabolites. Since tryptophan makes up 1%–2% of the total protein in many foods, there is the intriguing possibility that dietary proteins may regulate immunity by the AroA pathway. In humans, CD4 T cells that express IL-22 in the absence of IL-17 cytokines have been identified, supporting the possibility that these cells are regulatory in nature and are dedicated to the maintenance and repair of epithelial integrity. However, their role in normal and inflamed gut has not been established.
Notch signaling in spermatogenesis and male (in)fertility
Published in Rajender Singh, Molecular Signaling in Spermatogenesis and Male Infertility, 2019
Mahitha Sahadevan, Pradeep G. Kumar
In testes, the expression of notch receptor and ligands fluctuates between seminiferous epithelial cycles depending on extrinsic and intrinsic signals. Okada et al. reported that oscillation in the expression of jagged 1 in the Sertoli cells during the first wave of spermatogenesis is regulated by cross talk between cyclic adenosine monophosphate (cAMP) and tumor necrosis factor-α (TNF-α) signaling. The simultaneous addition of cAMP and TNF-α in an in vitro culture of Sertoli cells resulted in the suppression of jagged 1 ligand, indicating that cAMP has a dominating role over TNF-α in regulating this event (127,145,147). A recent study documented a new regulatory arm between notch signaling and aryl hydrocarbon receptor (AhR) in testes. Normally, AhR regulates various cellular events like cell proliferation and differentiation through interactions with other signaling pathways. In AhR−/– mice, a degenerative change occurred in the testes due to germ cell apoptosis that reduced the number of early spermatids, coinciding with downregulation of the notch receptor and its target genes (148). All of these studies provide strong evidence regarding the intertwining between major signaling pathways and notch.
Environmental toxicants on Leydig cell function
Published in C. Yan Cheng, Spermatogenesis, 2018
Leping Ye, Xiaoheng Li, Xiaomin Chen, Qingquan Lian, Ren-Shan Ge
Polychlorinated biphenyls (PCBs), pentachlorophenol (PCP), and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), dichlorodiphenyltrichloroethane (DTT), and methoxychlor are organochlorines. PCBs are widely used as dielectric and coolant fluids in electrical apparatus, carbonless copy paper, and in heat transfer fluids. There are over 200 PCB congeners. PCP is an organochlorine compound used as a pesticide and a disinfectant. TCDD is formed as a side product in organic synthesis and burning of organic materials. These chemicals may have a common mechanism of actions via aryl hydrocarbon receptor (AHR).
Sex differences in the association of measures of sexual maturation to common toxicants: Lead, dichloro-diphenyl-trichloroethane (DDT), dichloro-diphenyl-dichloroethylene (DDE), and polychlorinated biphenyls (PCBs)
Published in Annals of Human Biology, 2021
Casey N. West, Lawrence M. Schell, Mia V. Gallo
The epidemiological literature showing both agonistic and antagonistic effects of organochlorines suggests multiple pathways of effects. Dioxins may affect normal growth and development by binding to the aryl hydrocarbon receptor. Such binding impacts the aryl hydrocarbon receptor nuclear translocator (AhR/ARNT) complex that regulates genes involved in maturation (Schecter et al. 2006; Gore et al. 2015). For non-dioxin like PCBs that do not bind to the aryl hydrocarbon receptor other pathways may be involved. In adult male rats, Leydig cell LH receptor density is reduced by PCB exposure with decreased Leydig cell steroidogenesis and LH-stimulated T production (Murugesan et al. 2005). Human exposure to both PCBs and DDT was associated with increased sex hormone binding globulin and reduced testosterone and LH, suggesting an impact on the hypothalamic pituitary gonadal axis (Grandjean et al. 2012). (Please see Diamanti-Kandarakis et al. (2009) and Bourguignon et al. (2016) for more specific details on endocrine pathways of effect).
Rodent genetic models of Ah receptor signaling
Published in Drug Metabolism Reviews, 2021
Rachel H. Wilson, Christopher A. Bradfield
The aryl hydrocarbon receptor (AHR) is a central paradigm of modern toxicology (Bradshaw and Bell 2009; Zhou 2016). This ligand activated transcription factor is a member of the PER-ARNT-SIM (PAS) superfamily of environmental sensors and is essential for the adaptive metabolism of many xenobiotic compounds, including polycyclic aromatic hydrocarbons (PAHs) like benzo(a)pyrene (BaP). The AHR participates in this biology through the induction of phase I xenobiotic metabolizing enzymes including members of the cytochromes P450 family (e.g. Cyp1a1, Cyp1a2, and Cyp1b1) and phase II enzymes such as glucuronosyltransferase (Figure 1). In addition to adaptive metabolism, the AHR plays a central role in the toxicity of common polyhalogenated pollutants including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related polychlorinated and polybrominated biphenyls. The adaptive and toxic pathways often overlap, as AHR-mediated induction of detoxification enzymes like Cyp1a1 and Cyp1b1 metabolize ligands such as BaP to yield toxic diol epoxide intermediates (Gelboin 1980). The mechanism of AHR-mediated toxicity of other ligands, such as TCDD, remains unclear. The dependence of many widespread environmental pollutants on AHR activation has made this signaling pathway the focus of many toxicological studies (Figure 1). A testament to this interest is the observation that a literature search cross referencing ‘AHR’ and ‘toxicology’ yields over 2000 results (Web of Science, June 10 2020).
Reverse transcription-loop mediated isothermal amplification (RT-LAMP) assay for detection of AhR receptor responsive xenobiotics
Published in Toxicology Mechanisms and Methods, 2021
Deeksha Sharma, Payal Rani, Suneel Kumar Onteru, Partha Roy, Rakesh Kumar Tyagi, Surya Pratap Singh, Dheer Singh
The aryl hydrocarbon receptor (AhR) is a ligand-activated receptor involved in the induction of xenobiotic-metabolizing Cytochromes P4501A1 (CYP1A1) etc. TCDD is the most potent ligand of AhR (Mimura and Fujii-Kuriyama 2003). Therefore, in order to elucidate the effect of TCDD on 2 D cultured buffalo granulosa cells, we checked the expression of AHR, CYP1A1 and CYP1B1 gene in a dose and time dependent manner by RT-qPCR. TCDD increased the AHR mRNA expression in the granulosa cells after 6 and 12 h to up to 3.9 (p < 0.01) folds compared to control in a dose dependent manner (Figure 2(a)). Though, there was no significant change observed after 24 h of culture. Moreover, the expression of AHR was up-regulated with the highest levels after 6 h. Additionally, we checked the expression of CYP1A1 gene, which was significantly up-regulated after 6 and 12 but no effect after 24 h similarly like AHR (Figure 2(b)). Wereas, the CYP1B1 gene expression increased slightly after 6 and 12 h from 1.3 folds to 1.8 folds and no effect was observed after 24 h. TCDD majorly increased the CYP1A1 gene expression by 8.2 folds compared to control after 6 h at 10 pg/mL. With respect to these studies, we selected CYP1A1 gene for development of RT-LAMP at 10 pg/mL dose of TCDD after 6 h in granulosa cells.