Cigarette Smoke Condensate Extracts Induce IL-1-Beta Production from Rheumatoid Arthritis Patient-Derived Synoviocytes, but Not Osteoarthritis Patient-Derived Synoviocytes, Through Aryl Hydrocarbon Receptor-Dependent NF-Kappa-B Activation and Novel NF-Kappa-B Sites

2013 ◽  
Vol 33 (6) ◽  
pp. 297-307 ◽  
Author(s):  
Miki Adachi ◽  
Shosuke Okamoto ◽  
Satomi Chujyo ◽  
Tomohiro Arakawa ◽  
Megumi Yokoyama ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Rheumatoid Arthritis Patient ◽  
Aryl Hydrocarbon Receptor ◽  
Cigarette Smoke ◽  
Cigarette Smoke Condensate ◽  
Nf Kappa B ◽  
Aryl Hydrocarbon ◽  
Osteoarthritis Patient

scholarly journals Down-Regulation of p23 in Normal Lung Epithelial Cells Reduces Toxicities From Exposure to Benzo[a]pyrene and Cigarette Smoke Condensate via an Aryl Hydrocarbon Receptor-Dependent Mechanism

2018 ◽  
Vol 167 (1) ◽  
pp. 239-248 ◽  
Author(s):  
Jinyun Chen ◽  
Poonam Yakkundi ◽  
William K Chan
Keyword(s):  
Epithelial Cells ◽  
Aryl Hydrocarbon Receptor ◽  
Cigarette Smoke ◽  
Lung Epithelial Cells ◽  
Normal Lung ◽  
Cigarette Smoke Condensate ◽  
Down Regulation ◽  
Protein Levels ◽  
Aryl Hydrocarbon ◽  
Lung Epithelial

Abstract The aryl hydrocarbon receptor (AHR) is a ligand-activated signaling molecule which controls tumor growth and metastasis, T cell differentiation, and liver development. Expression levels of this receptor protein is sensitive to the cellular p23 protein levels in immortalized cancer cell lines. As little as 30% reduction of the p23 cellular content can suppress the AHR function. Here we reported that down-regulation of the p23 protein content in normal, untransformed human bronchial/tracheal epithelial cells to 48% of its content also suppresses the AHR protein levels to 54% of its content. This p23-mediated suppression of AHR is responsible for the suppression of (1) the ligand-dependent induction of the cyp1a1 gene transcription; (2) the benzo[a]pyrene- or cigarette smoke condensate-induced CYP1A1 enzyme activity, and (3) the benzo[a]pyrene and cigarette smoke condensate-mediated production of reactive oxygen species. Reduction of the p23 content does not alter expression of oxidative stress genes and production of PGE2. Down regulation of p23 suppresses the AHR protein levels in two other untransformed cell types, namely human breast MCF-10A and mouse immune regulatory Tr1 cells. Collectively, down-regulation of p23 suppresses the AHR protein levels in normal and untransformed cells and can in principle protect our lung epithelial cells from AHR-dependent oxidative damage caused by exposure to agents from environment and cigarette smoking.

scholarly journals Hydroquinone Exposure Worsens Rheumatoid Arthritis through the Activation of the Aryl Hydrocarbon Receptor and Interleukin-17 Pathways

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 929
Author(s):  
Cintia Scucuglia Heluany ◽  
Paula Barbim Donate ◽  
Ayda Henriques Schneider ◽  
André Luis Fabris ◽  
Renan Augusto Gomes ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Aryl Hydrocarbon Receptor ◽  
Cigarette Smoke ◽  
Cigarette Smoke Exposure ◽  
Interleukin 17 ◽  
Aryl Hydrocarbon ◽  
Tnf Α

Rheumatoid arthritis (RA) development is strongly associated with cigarette smoke exposure, which activates the aryl hydrocarbon receptor (AhR) as a trigger for Th17 inflammatory pathways. We previously demonstrated that the exposure to hydroquinone (HQ), one of the major compounds of cigarette tar, aggravates the arthritis symptomatology in rats. However, the mechanisms related to the HQ-related RA still remain elusive. Cell viability, cytokine secretion, and gene expression were measured in RA human fibroblast-like synoviocytes (RAHFLS) treated with HQ and stimulated or not with TNF-α. Antigen-induced arthritis (AIA) was also elicited in wild type (WT), AhR −/− or IL-17R −/− C57BL/6 mice upon daily exposure to nebulized HQ (25ppm) between days 15 to 21. At day 21, mice were challenged with mBSA and inflammatory parameters were assessed. The in vitro HQ treatment up-regulated TNFR1, TNFR2 expression, and increased ROS production. The co-treatment of HQ and TNF-α enhanced the IL-6 and IL-8 secretion. However, the pre-incubation of RAHFLS with an AhR antagonist inhibited the HQ-mediated cell proliferation and gene expression profile. About the in vivo approach, the HQ exposure worsened the AIA symptoms (edema, pain, cytokines secretion and NETs formation) in WT mice. These AIA effects were abolished in HQ-exposed AhR −/− and IL-17R −/− animals though. Our data demonstrated the harmful HQ influence over the onset of arthritis through the activation and proliferation of synoviocytes. The HQ-related RA severity was also associated with the activation of AhR and IL-17 pathways, highlighting how cigarette smoke compounds can contribute to the RA progression.

scholarly journals Aryl hydrocarbon receptor (AhR)-dependent regulation of pulmonary miRNA by chronic cigarette smoke exposure

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Sarah Rogers ◽  
Angela Rico de Souza ◽  
Michela Zago ◽  
Matthew Iu ◽  
Necola Guerrina ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Cigarette Smoke ◽  
Smoke Exposure ◽  
Cigarette Smoke Exposure ◽  
Aryl Hydrocarbon

scholarly journals Inhibition of dioxin effects on bone formation in vitro by a newly described aryl hydrocarbon receptor antagonist, resveratrol

2000 ◽  
Vol 167 (1) ◽  
pp. 183-195 ◽  
Author(s):  
SU Singh ◽  
RF Casper ◽  
PC Fritz ◽  
B Sukhu ◽  
B Ganss ◽  
...  
Keyword(s):  
Periodontal Disease ◽  
Aryl Hydrocarbon Receptor ◽  
Cigarette Smoke ◽  
Bone Cell ◽  
Nodule Formation ◽  
Antifungal Compound ◽  
Type I ◽  
Aryl Hydrocarbon

Aryl hydrocarbon receptor (AhR) ligands are environmental contaminants found in cigarette smoke and other sources of air pollution. The prototypical compound is TCDD (2,3,7, 8-tetrachlorodibenzo-p-dioxin), also known as dioxin. There is an increasing body of knowledge linking cigarette smoking to osteoporosis and periodontal disease, but the direct effects of smoke-associated aryl hydrocarbons on bone are not well understood. Through the use of resveratrol (3,5,4'-trihydroxystilbene), a plant antifungal compound that we have recently demonstrated to be a pure AhR antagonist, we have investigated the effects of TCDD on osteogenesis. It was postulated that TCDD would inhibit osteogenesis in bone-forming cultures and that this inhibition would be antagonized by resveratrol. We employed the chicken periosteal osteogenesis (CPO) model, which has been shown to form bone in vitro in a pattern morphologically and biochemically similar to that seen in vivo, as well as a rat stromal cell bone nodule formation model. In the CPO model, alkaline phosphatase (AP) activity was reduced by up to 50% (P<0.01 vs control) in the presence of 10(-9) M TCDD and these effects were reversed by 10(-6) M resveratrol (P<0.05 vs TCDD alone). TCDD-mediated inhibition of osteogenesis was restricted primarily to the osteoblastic differentiation phase (days 0-2) as later addition did not appear to have any effects. Message levels for important bone-associated proteins (in the CPO model) such as collagen type I, osteopontin, bone sialoprotein and AP were inhibited by TCDD, an effect that was antagonized by resveratrol. Similar findings were obtained using the rat stromal bone cell line. TCDD (at concentrations as low as 10(-10)M) caused an approximately 33% reduction in AP activity, which was abrogated by 3. 5x10(-7) M resveratrol. TCDD also induced a marked reduction in mineralization ( approximately 75%) which was completely antagonized by resveratrol. These data suggest that AhR ligands inhibit osteogenesis probably through inhibition of osteodifferentiation and that this effect can be antagonized by resveratrol. Since high levels of AhR ligands are found in cigarette smoke, and further since smoking is an important risk factor in both osteoporosis and periodontal disease, it may be postulated that AhR ligands are the component of cigarette smoke linking smoking to osteoporosis and periodontal disease. If so, resveratrol could prove to be a promising preventive or therapeutic agent for smoking-related bone loss.

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