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

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Heluany, Cintia Scucuglia ^[1] ; Donate, Paula Barbim ^[2] ; Schneider, Ayda Henriques ^[2] ; Fabris, Andre Luis ^{[1, 3]} ; Gomes, Renan Augusto ; Villas-Boas, Isadora Maria ^[4] ; Tambourgi, Denise Vilarinho ^[4] ; da Silva, Tarcilia Aparecida ^[5] ; Trossini, Gustavo Henrique Goulart ^[3] ; Nalesso, Giovanna ^[6] ; Silveira, Eduardo Lani Volpe ^[1] ; Cunha, Fernando Queiroz ^[2] ; Farsky, Sandra Helena Poliselli ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin & Toxicol Analyses, BR-05508000 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, BR-14049900 Ribeirao Preto - Brazil

^[3] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Pharm, BR-05508000 Sao Paulo - Brazil

^[4] Butantan Inst, Immunochemistry Lab, BR-05503900 Sao Paulo - Brazil

^[5] Univ Fed Minas Gerais, Sch Dent, Dept Oral Surg & Pathol, BR-3127090 Belo Horizonte, MG - Brazil

^[6] Univ Surrey, Sch Vet Med, Dept Pre Clin Sci, Guildford GU2 7AL, Surrey - England

• Tipo de documento: Artigo Científico
• Fonte: ANTIOXIDANTS; v. 10, n. 6 JUN 2021.
• Citações Web of Science: 0

Resumo

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-alpha. 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-alpha 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. (AU)

• Processo FAPESP: 19/19573-7 - Efeitos da exposição ao vapor aquecido do tabaco sobre a Artrite Reumatóide
• Beneficiário: Sandra Helena Poliselli Farsky
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/07328-4 - Identificação de vias endógenas para o controle da inflamação
• Beneficiário: Sandra Helena Poliselli Farsky
• Modalidade de apoio: Auxílio à Pesquisa - Temático