Involvement of purinergic signaling on nitric oxide production by neutrophils stimulated with Trichomonas vaginalis

Frasson, Amanda Piccoli; Carli, Geraldo Attílio De; Bonan, Carla Denise; Tasca, Tiana

doi:10.1007/s11302-011-9254-7

Cited by 19 publications

(19 citation statements)

References 48 publications

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“…In general, the anti-inflammatory effects of adenosine are attributed to A2A receptor based on its ability to increase cAMP accumulation [43]. The involvement of this receptor subtype was also observed in one previous study of our group where A2A was associated with reduction of NO production by T. vaginalis-stimulated neutrophils [11]. In the present study, the participation of A1 receptor was suggested by the overexpression of the receptor fluorescence in the presence of increased adenosine bioavailability.…”

Section: Discussionsupporting

confidence: 86%

“…Considering the involvement of purinergic signaling on this immune mechanism, the presence of nucleotides did not regulate the release of the mediator. Previous work from our group has already demonstrated the participation of nucleotides and nucleosides on the NO secretion by T. vaginalis-stimulated neutrophils [11]. Interestingly, the nucleoside adenosine by itself was not able to modulate ROS production by T. vaginalis-stimulated neutrophils.…”

Section: Discussionmentioning

confidence: 73%

“…T. vaginalis has already shown to be able to stimulate the production of a variety of chemoattractants by neutrophils, such as superoxide anions [10] nitric oxide (NO) [11] and interleukin-8 (IL-8) [12]. Furthermore, it has been demonstrated that T. vaginalis trophozoites and their secreted products are capable of producing leukotriene B4 [13], which leads the production of IL-8 by neutrophils and mast cells [14,15].…”

Section: Introductionmentioning

confidence: 99%

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

Frasson

Menezes

Goelzer

et al. 2017

Purinergic Signalling

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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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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 73%

Section: Introductionmentioning

confidence: 99%

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

Frasson

Menezes

Goelzer

et al. 2017

Purinergic Signalling

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“…Neutrophils exposed to Trichomonas vaginalis produced nitric oxide and interleukin-8. 90,91 Interleukin-8 along with the other cytokines can, in turn, stimulate NO synthesis.…”

Section: Protozoan Parasites Initiate the Development Of Finger-like mentioning

confidence: 99%

Membrane tubulovesicular extensions (cytonemes)

Galkina

Федорова

Stadnichuk

et al. 2013

Cell Adhesion & Migration

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“…On the contrary, nucleosides as adenosine, often suppress the inflammatory response, limiting local and systemic inflammation . In T. vaginalis , this enzymatic cascade has already been characterized with the presence of nucleoside triphosphate diphosphohydrolase (NTPDase) and ecto‐5′‐nucleotidase enzymes, and it seems to be involved in mediating immune aspects during infection …”

Section: Introductionmentioning

confidence: 99%

The anti‐Trichomonas vaginalis phloroglucinol derivative isoaustrobrasilol B modulates extracellular nucleotide hydrolysis

et al. 2017

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Trichomonas vaginalis causes trichomoniasis, a neglected sexually transmitted disease. Due to severe health consequences and treatment failure, new therapeutic alternatives are crucial. Phloroglucinols from southern Brazilian Hypericum species demonstrated anti-T. vaginalis and anti-Leishmania amazonensis activities. The modulation of biochemical pathways involved in the control of inflammatory response by ectonucleotidases, NTPDase, and ecto-5'-nucleotidase represents new targets for combating protozoa. This study investigated the activity of phloroglucinol derivatives of Hypericum species from southern Brazil against T. vaginalis as well as its ability on modulating parasite ectonucleotidases and, consequently, immune parameters through ATP and adenosine effects. Phloroglucinol derivatives screening revealed activity for isoaustrobrasilol B (IC 38 μm) with no hemolytic activity. Although the most active compound induced cytotoxicity against a mammalian cell lineage, the in vivo model evidenced absence of toxicity. Isoaustrobrasilol B significantly inhibited NTPDase and ecto-5'-nucleotidase activities, and the immune modulation attributed to extracellular nucleotide accumulation was evaluated. The production of ROS and IL-6 by T. vaginalis-stimulated neutrophils was not affected by the treatment. Conversely, IL-8 levels were significantly enhanced. The associative mechanism of trophozoites death and ectonucleotidases modulation by isoaustrobrasilol B may increase the susceptibility of T. vaginalis to host innate immune cell like neutrophils consequently, contributing to parasite clearance.

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Involvement of purinergic signaling on nitric oxide production by neutrophils stimulated with Trichomonas vaginalis

Cited by 19 publications

References 48 publications

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

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

Membrane tubulovesicular extensions (cytonemes)

The anti‐Trichomonas vaginalis phloroglucinol derivative isoaustrobrasilol B modulates extracellular nucleotide hydrolysis

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