Original ResearchFull Report: Basic and Translational—PancreasAryl Hydrocarbon Receptor Ligands in Cigarette Smoke Induce Production of Interleukin-22 to Promote Pancreatic Fibrosis in Models of Chronic Pancreatitis
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Mice and Treatments
All animal protocols were approved by Institutional Animal Care and Use Committees of Stanford University. All mice including Balb/c, C57BL/6J, and AhRd were purchased from Jackson Laboratory (Bar Harbor, ME) and were housed under pathogen-free conditions. Experimental mice were age- and sex-matched. Bone marrow (BM) chimeric mice were generated by lethally irradiating mice with 9.5 Gy γ-radiation in 2 doses approximately 3 hours apart, followed by intravenous injection of 5 × 106 BM cells from
Aryl Hydrocarbon Receptor Activation Worsens Fibrosis in Chronic Pancreatitis
Cigarette smoking is an independent risk factor for accelerating CP,6, 9 however, the mechanism remains elusive. Cigarette smoke contains AhR agonists, such as dioxin and BaP10, 11; in addition, cigarette smoke was found to have an unexpectedly high dioxin-like potential that triggers AhR activation.12 Therefore, we sought to investigate the role of cigarette smoke AhR ligands on immune activation and on the pathogenesis of CP.
The well-characterized potent AhR agonist TCDD was administrated to
Discussion
CP is a complex chronic inflammation disorder with links to genetic, metabolic, and environmental factors. Alcohol is the most established environmental risk factor for CP, while the independent effects and risks associated with smoking have not been elucidated until recently. In most populations, smoking is strongly associated with drinking alcohol,25 therefore, the independent effect of smoking can be difficult to assess. However, data from case-control26 and population-based studies5, 27
Acknowledgments
The authors thank Wenjun Ouyang from Genentech for providing anti-IL22 antibody. The authors thank Yi Wei for technical assistance.
Jing Xue and Qinglan Zhao contributed equally to this work. Walter Park and Aida Habtezion contributed equally to this work.
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2023, Progress in Retinal and Eye ResearchCitation Excerpt :AhR is a member of the family of basic helix-loop-helix transcription factors and though not a traditional nuclear receptor, shares transcriptional similarities. The AhR is of great interest as it can be activated by components of cigarette smoke, relevant, as smoking is a major risk factor for AMD development and progression (Xue et al., 2016). Additionally, the activity of this receptor declines with age (Hu et al., 2013).
Conflicts of interest The authors disclose no conflicts.
Funding This work was supported by the National Pancreas Foundation Grant, National Institute of Health (NIH) grants DK092421 and DK105263 (Aida Habtezion); National Natural Science Foundation of China grant, China State Key Laboratory of Oncogenes and Related Gene (no. 91-15-15), Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning (no. TP2015007) (Jing Xue); Department of Veterans Affairs, and NIH CA163200 (Stephen J. Pandol), AA019996 and AA011999 (Stephen J. Pandol and Mouad Edderkaoui).
Author names in bold designate shared co-first authorship.
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Authors share co-first authorship.