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

Heluany, Cintia Scucuglia and Donate, Paula Barbim and Schneider, Ayda Henriques and Fabris, André Luis and Gomes, Renan Augusto and Villas-Boas, Isadora Maria and Tambourgi, Denise Vilarinho and Silva, Tarcilia Aparecida da and Trossini, Gustavo Henrique Goulart and Nalesso, Giovanna and Silveira, Eduardo Lani Volpe and Cunha, Fernando Queiroz and Farsky, Sandra Helena Poliselli (2021) Hydroquinone Exposure Worsens Rheumatoid Arthritis through the Activation of the Aryl Hydrocarbon Receptor and Interleukin-17 Pathways. Antioxidants, 10 (6). p. 929. ISSN 2076-3921

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Abstract

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.

Item Type: Article
Subjects: STM Academic > Agricultural and Food Science
Depositing User: Unnamed user with email support@stmacademic.com
Date Deposited: 12 Oct 2023 07:04
Last Modified: 12 Oct 2023 07:04
URI: http://article.researchpromo.com/id/eprint/1322

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