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Lack of Annexin A1 Exacerbates Inflammatory Response in Acute Endometritis Model

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Abstract

Annexin A1 (AnxA1) is a glucocorticoid-inducible protein and an important endogenous modulator of inflammation. However, its effect in the endometrial microenvironment is poorly explained. This study aimed to evaluate the role of endogenous AnxA1 in an endometritis mouse model induced by lipopolysaccharide (LPS). Female C57BL/6 wild-type (WT) and AnxA1−/− mice were divided into two groups: SHAM and LPS. To induce endometritis, mice received a vaginal infusion of 50 μL of LPS (1 mg/mL) dissolved in phosphate-buffered saline. After 24 h, the mice were euthanized, and blood and uteri samples were collected. The endometrium inflammatory scores were significantly increased in the LPS-treated group. AnxA1−/− mice from the LPS group demonstrated a significant increase in the number of degranulated mast cell levels compared to AnxA1−/− SHAM mice. The Western blotting analysis revealed that a lack of AnxA1 promoted the upregulation of NLRP3 and pro-IL-1β in the acute endometritis animal model compared to WT LPS animals. LPS-induced endometritis increased the number of blood peripheral leukocytes in both WT and AnxA1−/− mice compared with SHAM group mice (p < 0.001). AnxA1−/− mice also showed increased plasma levels of IL-1β (p < 0.01), IL-6, IL-10, IL-17, and TNF-α (p < 0.05) following LPS-induced endometritis. In conclusion, a lack of endogenous AnxA1 exacerbated the inflammatory response in an endometritis model via NLRP3 dysregulation, increased uterine mast cell activation, and plasma pro-inflammatory cytokine release.

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Data Availability

The data that support the findings of this study are available from the corresponding author, upon reasonable request.

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Acknowledgements

This research was funded by the Fundação ao de Amparo à Pesquisa do Estado de São Paulo - FAPESP [grant number 22/02327-6]. RRV was supported by the Coordenação ao de Aperfeiçoamento de Pessoal de Nível Superior (CAPES-Finance code 001) scholarship. CDG is a researcher fellow of the Conselho Nacional de Desenvolvimento Científico e Tecnologico (CNPq). AAFC was supported by the CAPES-Print scholarship.

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Author notes

  1. Cristiane D. Gil and Adriana A. F. Carbonel share senior authorship of this manuscript.

Authors and Affiliations

  1. Department of Morphology and Genetics, Universidade Federal de São Paulo, Rua Botucatu 740, Edifício Lemos Torres – 3° andar, São Paulo, SP, 04023-900, Brazil

    Renata R. Vieira, Gisela R. S. Sasso, Paulo C. Franco, Cristiane D. Gil & Adriana A. F. Carbonel

  2. Biosciences Graduate Program, Institute of Biosciences, Letters and Exact Sciences, Universidade Estadual Paulista (UNESP), São José do Rio Preto, Brazil

    Rafael André da Silva & Cristiane D. Gil

  3. Department of Medicine, Nephrology Division, Universidade Federal de São Paulo (UNIFESP), Sao Paulo, SP, 04038-901, Brazil

    Fernanda T. Borges

  4. Queen’s Cardiopulmonary Unit (QCPU), Queen’s University, Kingston, ON, K7L 3N6, Canada

    Patrícia D. A. Lima

  5. School of Medicine, Universidade do Oeste Paulista (UNOESTE), Guaruja, SP, 11441-225, Brazil

    Jose Marcos Sanches

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Contributions

Conceptualization: RRV, CDG, AAFC; Methodology: RRV, RAS, GRSS, PCF, FTB, JMS; Formal analysis: RRV, RAS, PL, CDG, AAFC. Investigation and Data curation: RRV. Writing-original draft preparation: RRV, JMS; Writing-review and editing: PL, CDG, AAFC. Project administration and Funding acquisition: CDG; Supervision: CDG, AAFC.

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Correspondence to Cristiane D. Gil.

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Vieira, R.R., da Silva, R.A., Sasso, G.R.S. et al. Lack of Annexin A1 Exacerbates Inflammatory Response in Acute Endometritis Model. Inflammation (2024). https://doi.org/10.1007/s10753-023-01959-3

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  • DOI: https://doi.org/10.1007/s10753-023-01959-3

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