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Adenosine reduces reactive oxygen species and interleukin-8 production by Trichomonas vaginalis-stimulated neutrophils

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Abstract

Trichomonas vaginalis is a flagellated protozoan that affects the human urogenital tract causing 276.4 million new infections a year. The parasite elicits a vaginal mucosal infiltration of immune cells, especially neutrophils which are considered to be primarily responsible for cytological change observed at the infection site as well as the major contributor in the inflammatory response against the parasite. Extracellular nucleotides and their nucleosides are signaling compounds involved in several biological processes, including inflammation and immune responses. Once in the extracellular space, the nucleotides and nucleosides can directly activate the purinergic receptors. Herein, we investigated the involvement of purinergic signaling on the production of reactive oxygen species (ROS) and cytokines by T. vaginalis-stimulated neutrophils. Parasites were able to induce an increase in ROS and IL-8 levels while they did not promote IL-6 secretion or neutrophil elastase activity. Adenine and guanine nucleotides or nucleosides were not able to modulate ROS and cytokine production; however, when T. vaginalis-stimulated neutrophils were incubated with adenosine and adenosine deaminase inhibitor, the levels of ROS and IL-8 were significantly reduced. These immunosuppressive effects were probably a response to the higher bioavailability of adenosine found in the supernatant as result of inhibition of enzyme activity. The involvement of P1 receptors was investigated by immunofluorescence and A1 receptor was the most abundant. Our data show that the influence of purinergic signaling, specifically those effects associated with adenosine accumulation, on the modulation of production of proinflammatory mediators by T. vaginalis-stimulated neutrophils contribute to the understanding of immunological aspects of trichomoniasis.

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Acknowledgements

Authors thank Centro de Microscopia e Microanálise, CMM/UFRGS, for technical assistance in the confocal microscopy.

Funding

This work was supported by the NANOBIOTEC-Brazil program from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brazil (grant 23038.019022/2009-68) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brazil (grant 474930/2012-2). A.P.F. and C.B.M are recipients of Ph.D. fellowships from CAPES/Brazil. T.T. thanked CNPq/Brazil for research fellowship (grant 307447/2014-6).

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Authors and Affiliations

  1. Laboratório de Pesquisa em Parasitologia, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Av. Ipiranga 2752, Porto Alegre, RS, 90610-000, Brazil

    Amanda Piccoli Frasson, Camila Braz Menezes & Tiana Tasca

  2. Laboratório de Toxicologia, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Av. Ipiranga 2752, Porto Alegre, RS, 90610-000, Brazil

    Gustavo Krumel Goelzer & Solange Cristina Garcia

  3. Laboratório de Fitoquímica e Síntese Orgânica, Programa de Pós-graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Av. Ipiranga 2752, Porto Alegre, RS, 90610-000, Brazil

    Simone Cristina Baggio Gnoatto

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  1. Amanda Piccoli Frasson
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  2. Camila Braz Menezes
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Correspondence to Tiana Tasca.

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Amanda Piccoli Frasson declares that she has no conflict of interest.

Camila Braz Menezes declares that she has no conflict of interest.

Gustavo Krumel Goelzer declares that he has no conflict of interest.

Simone Cristina Baggio Gnoatto declares that she has no conflict of interest.

Solange Cristina Garcia declares that she has no conflict of interest.

Tiana Tasca declares that she has no conflict of interest.

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Human neutrophils were collected from venous blood of healthy volunteers with ethical approved by UFRGS Ethical Committee, number 19346.

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Frasson, A.P., Menezes, C.B., Goelzer, G.K. et al. Adenosine reduces reactive oxygen species and interleukin-8 production by Trichomonas vaginalis-stimulated neutrophils. Purinergic Signalling 13, 569–577 (2017). https://doi.org/10.1007/s11302-017-9584-1

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