Abstract
Background
The interaction of Cryptococcus neoformans with airway epithelial cells is crucial for the establishment of cryptococcosis. Aspirin-triggered-resolvin D1 (AT-RvD1) is a lipid mediator produced during the resolution of inflammation and demonstrates anti-inflammatory and pro-resolution effects in several inflammatory experimental models including in the airways.
Method
Here, we evaluated the effects of AT-RvD1 (1, 10 or 100 nM) on human bronchial epithelial cells (BEAS-2B) stimulated with C. neoformans (1, 10 or 100 multiplicities of infection; MOI).
Results
After 24 h, C. neoformans (all MOI) demonstrated no cytotoxic effects and increased IL-8 production on BEAS-2B cells when compared to controls. In addition, C. neoformans (MOI 100) increased the concentration of IL-6, but not of IL-10. AT-RvD1 (100 nM) significantly reduced the concentration of IL-8 and IL-6 and increased IL-10 production in C. neoformans-stimulated BEAS-2B cells. C. neoformans increased the phosphorylation of NF-κB and ERK1/2, and ALX/FPR2 expression. AT-RvD1 reduced the activation of NF-kB without altering the ERK1/2 and ALX/FPR2 expression. The anti-inflammatory effects of AT-RvD1 were dependent on the ALX/FPR2, once its antagonist (BOC2) reversed its anti-inflammatory effects. No alteration on the fungal burden as well as interactions with BEAS-2B cells was observed by AT-RvD1.
Conclusion
AT-RvD1 demonstrated significant anti-inflammatory effects in bronchial epithelial cells infected with C. neoformans without affecting the development of C. neoformans infection in the airways.
Trial registration
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Acknowledgements
This work was supported by Grants from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) (No. 475349/2010-5), Fundação de Apoio a Pesquisa do Estado de Minas Gerais (FAPEMIG; APQ 01631/11 e APQ-01873-14). Rede de Pesquisa em Doenças Infecciosas Humanas e Animais do Estado de Minas Gerais and Universidade Federal do Triângulo Mineiro (UFTM), Brazil. This study was also financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001.
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Salerno, B.S., Pereira, A.B.M., de Souza, H.I. et al. Anti-inflammatory actions of aspirin-triggered resolvin D1 (AT-RvD1) in bronchial epithelial cells infected with Cryptococcus neoformans. Inflammopharmacol 29, 1603–1612 (2021). https://doi.org/10.1007/s10787-021-00855-2
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DOI: https://doi.org/10.1007/s10787-021-00855-2