Estradiol replacement therapy regulates innate immune response in ovariectomized arthritic mice

Author(s)

Schneider, Ayda Henriques ^{[1, 2]} ; Kanashiro, Alexandre ^[3] ; Veloso Dutra, Sabrina Graziani ^[2] ; de Souza, Raquel do Nascimento ^[2] ; Veras, Flavio Protasio ^[1] ; Cunha, Fernando de Queiroz ^[1] ; Ulloa, Luis ^[4] ; Mecawi, Andre Souza ^{[2, 5]} ; Reis, Luis Carlos ^[2] ; Malvara, David do Carmo ^[2]

Affiliation

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Univ Fed Rural Rio de Janeiro, Dept Physiol Sci, Multicentr Program Postgrad Physiol Sci, BR 465 Km 07, BR-23897000 Seropedica, RJ - Brazil

^[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Neurosci & Behav, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil

^[4] Rutgers State Univ, Ctr Immunol & Inflammat, New Jersey Med Sch, Dept Surg, Newark, NJ 07103 - USA

^[5] Univ Fed Sao Paulo, Paulista Sch Med, Dept Biophys, Rua Botucatu 862, BR-04023062 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: International Immunopharmacology; v. 72, p. 504-510, JUL 2019.
• Web of Science Citations: 0

Abstract

Neuroendocrine changes are essential factors contributing to the progression and development of rheumatoid arthritis. However, the role of estrogen in the innate immunity during arthritis development is still controversial. Here, we evaluated the effect of estrous cycle, ovariectomy, estradiol replacement therapy and treatment with estrogen receptor (ER)alpha and ER beta specific agonists on joint edema formation, neutrophil recruitment, and articular levels of cytokines/chemokines in murine zymosan-induced arthritis. Our results showed that articular inflammation of proestus/estrus was similar to metaestus/diestrus animals indicating that the inflammatory response in acute arthritis is not affected by the estrous cycle. However, ovariectomy increased joint swelling, neutrophil migration, and TNF-alpha level. Treatment for six consecutive days with estradiol cypionate re-established the acute inflammation in ovariectomized arthritic mice to responses similar to those in SHAM-proestrus/estrus or naive mice. Moreover, treatment with propylpyrazoletriol and diarylpropionitrile, two ER alpha and ER beta selective agonists, respectively, inhibited both edema and neutrophil recruitment. Finally, the non-genomic properties of estradiol were analyzed with an acute treatment with beta-estradiol-water soluble, which reduced the edema only. In the present study, estradiol replacement therapy improves the innate immune responses in ovariectomized arthritic mice by activating nuclear estrogen receptors. These results suggest that estradiol can induce a protective anti-inflammatory effect in arthritis during ovaries failure, as observed in the menopause. (AU)

• FAPESP's process: 11/20343-4 - Antiinflammatory cholinergic pathway: the role of neuroimmunomodulation in the control of inflammatory response
• Grantee: Alexandre Kanashiro
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases
• Grantee: Fernando de Queiroz Cunha
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 12/04237-2 - Antiinflammatory Cholinergic Pathway: The role of neuroimmunomodulation in the control of inflammatory response.
• Grantee: Alexandre Kanashiro
• Support Opportunities: Scholarships in Brazil - Young Researchers