Estradiol replacement therapy regulates innate immune response in ovariectomized arthritic mice

Ayda Henriques Schneider, Alexandre Kanashiro, Sabrina Graziani Veloso Dutra, Raquel do Nascimento de Souza, Flávio Protásio Veras, Fernando de Queiroz Cunha, Luis Ulloa, André Souza Mecawi, Luis Carlos Reis, David do Carmo Malvar

Research output: Contribution to journalArticle

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)α and ERβ 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-α 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 ERα and ERβ selective agonists, respectively, inhibited both edema and neutrophil recruitment. Finally, the non-genomic properties of estradiol were analyzed with an acute treatment with β-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.

Original languageEnglish (US)
Pages (from-to)504-510
Number of pages7
JournalInternational Immunopharmacology
Volume72
DOIs
StatePublished - Jul 1 2019

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Innate Immunity
Arthritis
Estradiol
Joints
Estrogen Receptors
Edema
Estrogens
Estrous Cycle
Neutrophil Infiltration
Estrus
Ovariectomy
Therapeutics
Inflammation
Diestrus
Proestrus
Zymosan
Menopause
Chemokines
Ovary
Rheumatoid Arthritis

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Pharmacology

Keywords

  • Arthritis
  • Endocrinology
  • Estrogen
  • Inflammation
  • Neutrophil

Cite this

Schneider, A. H., Kanashiro, A., Dutra, S. G. V., de Souza, R. D. N., Veras, F. P., Cunha, F. D. Q., ... Malvar, D. D. C. (2019). Estradiol replacement therapy regulates innate immune response in ovariectomized arthritic mice. International Immunopharmacology, 72, 504-510. https://doi.org/10.1016/j.intimp.2019.04.048
Schneider, Ayda Henriques ; Kanashiro, Alexandre ; Dutra, Sabrina Graziani Veloso ; de Souza, Raquel do Nascimento ; Veras, Flávio Protásio ; Cunha, Fernando de Queiroz ; Ulloa, Luis ; Mecawi, André Souza ; Reis, Luis Carlos ; Malvar, David do Carmo. / Estradiol replacement therapy regulates innate immune response in ovariectomized arthritic mice. In: International Immunopharmacology. 2019 ; Vol. 72. pp. 504-510.
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Schneider, AH, Kanashiro, A, Dutra, SGV, de Souza, RDN, Veras, FP, Cunha, FDQ, Ulloa, L, Mecawi, AS, Reis, LC & Malvar, DDC 2019, 'Estradiol replacement therapy regulates innate immune response in ovariectomized arthritic mice', International Immunopharmacology, vol. 72, pp. 504-510. https://doi.org/10.1016/j.intimp.2019.04.048

Estradiol replacement therapy regulates innate immune response in ovariectomized arthritic mice. / Schneider, Ayda Henriques; Kanashiro, Alexandre; Dutra, Sabrina Graziani Veloso; de Souza, Raquel do Nascimento; Veras, Flávio Protásio; Cunha, Fernando de Queiroz; Ulloa, Luis; Mecawi, André Souza; Reis, Luis Carlos; Malvar, David do Carmo.

In: International Immunopharmacology, Vol. 72, 01.07.2019, p. 504-510.

Research output: Contribution to journalArticle

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AU - Schneider, Ayda Henriques

AU - Kanashiro, Alexandre

AU - Dutra, Sabrina Graziani Veloso

AU - de Souza, Raquel do Nascimento

AU - Veras, Flávio Protásio

AU - Cunha, Fernando de Queiroz

AU - Ulloa, Luis

AU - Mecawi, André Souza

AU - Reis, Luis Carlos

AU - Malvar, David do Carmo

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Y1 - 2019/7/1

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