miR-294 and miR-410 Negatively Regulate Tnfa, Arginine Transporter Cat1/2, and Nos2 mRNAs in Murine Macrophages Infected with Leishmania amazonensis

Acuña, Stephanie Maia; Zanatta, Jonathan Miguel; Bento, Camilla de Almeida; Flöeter-Winter, Lucile Maria; Muxel, Sandra Márcia

doi:10.3390/ncrna8010017

Cited by 6 publications

(6 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…With these facts in mind, we attempted to study the expression of macrophage metabolism-related genes upon supplementation with putrescine, spermidine and spermine, with or without L-arginine during infection. After L- We have already reported that higher levels of citrulline in BALB/c and C57BL/6 macrophages after 4h of infection with L. amazonensis did not correlate with NO production, once the NO production was observed only in C57BL/6 macrophages (35,45,47). We now showed that the supplementation with putrescine increased Nos2 levels, but did not reflect in increased NO production.…”

Section: Discussionmentioning

confidence: 56%

“…We have already reported that higher levels of citrulline in BALB/c and C57BL/6 macrophages after 4h of infection with L. amazonensis did not correlate with NO production, once the NO production was observed only in C57BL/6 macrophages (35,45,47). We now showed that the supplementation with putrescine increased Nos2 levels, but did not reflect in increased NO production.…”

Section: Discussionmentioning

confidence: 87%

See 1 more Smart Citation

Polyamines shift expression of macrophage L-arginine metabolism related-genes during Leishmania amazonensis infection

Zanatta

Acuña

Bento

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Polyamines are molecules involved in macrophage activation and polarization in response to pathogens. The interaction with Leishmania promotes modulation of macrophage immune response to favor arginine deviation to polyamines production, leading to parasite survival. Polyamine levels are a potential modulator of growth factors, driving cells to proliferation, wound healing, oxidative stress, or regulating translation . Here, we investigate the impact of L-arginine and polyamines in the transcriptional regulation of genes involved in arginine metabolization and pro-inflammatory response to L. amazonensis in murine BALB/c macrophages. We found that supplementation with L-arginine is insufficient to modulate macrophage gene expression and infection. Polyamine supplementation altered nitric oxide synthase (Nos2) and nitric oxide (NO) production, as well as other macrophage enzymes. Putrescine supplementation increased transcript levels of polyamine metabolism-related genes Arginase 2 (Arg2), Spermidine synthase (SpdS), and Spermine synthase (SpmS) in both uninfected and L. amazonensis infected macrophages. Putrescine increased Nos2 expression without leading to NO production, while L-arginine plus spermine led to production of NO in uninfected macrophages. Besides, L-arginine supplementation reduced the levels of Il-1b during infection, and L-arginine or L-arginine plus putrescine increased Mcp1 at 24h of infection. The percentage of infected macrophages was lower after putrescine, spermidine, and spermine supplementation than L-arginine supplementation. Our data showed that the polyamines shift L-arginine-metabolism related-genes on BALB/c macrophages and affect infection by L. amazonensis.

show abstract

Section: Discussionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 87%

Polyamines shift expression of macrophage L-arginine metabolism related-genes during Leishmania amazonensis infection

Zanatta

Acuña

Bento

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…skin lesions, probably by the low O 2 pressure in the micromilieu [65]. However, we have already reported NO production in L. amazonensis infected C57BL/6 macrophages [39,50,66]. NO-producing cells were observed in L-arginine plus spermine supplementation in L. amazonensis-infected macrophages without Nos2 modulation.…”

Section: Plos Onementioning

confidence: 77%

Putrescine supplementation shifts macrophage L-arginine metabolism related-genes reducing Leishmania amazonensis infection

et al. 2023

Self Cite

View full text Add to dashboard Cite

Leishmania is a protozoan that causes leishmaniasis, a neglected tropical disease with clinical manifestations classified as cutaneous, mucocutaneous, and visceral leishmaniasis. In the infection context, the parasite can modulate macrophage gene expression affecting the microbicidal activity and immune response. The metabolism of L-arginine into polyamines putrescine, spermidine, and spermine reduces nitric oxide (NO) production, favoring Leishmania survival. Here, we investigate the effect of supplementation with L-arginine and polyamines in infection of murine BALB/c macrophages by L. amazonensis and in the transcriptional regulation of genes involved in arginine metabolism and proinflammatory response. We showed a reduction in the percentage of infected macrophages upon putrescine supplementation compared to L-arginine, spermidine, and spermine supplementation. Unexpectedly, deprivation of L-arginine increased nitric oxide synthase (Nos2) gene expression without changes in NO production. Putrescine supplementation increased transcript levels of polyamine metabolism-related genes Arg2, ornithine decarboxylase (Odc1), Spermidine synthase (SpdS), and Spermine synthase (SpmS), but reduced Arg1 in L. amazonensis infected macrophages, while spermidine and spermine promoted opposite effects. Putrescine increased Nos2 expression without leading to NO production, while L-arginine plus spermine led to NO production in uninfected macrophages, suggesting that polyamines can induce NO production. Besides, L-arginine supplementation reduced Il-1b during infection, and L-arginine or L-arginine plus putrescine increased Mcp1 at 24h of infection, suggesting that polyamines availability can interfere with cytokine/chemokine production. Our data showed that putrescine shifts L-arginine-metabolism related-genes on BALB/c macrophages and affects infection by L. amazonensis.

show abstract

“…We showed here that, although early stages of photo-oxidative damage (1-day) do not show substantial histological changes, there are already detectable miRNA changes in the circulation. These miRNAs included miR-128a-3p, miR-200b-3p, miR-410-3p and miR-218-5p, which have shown to be involved in inflammation and oxidative stress processes and to play a role in neurodegenerative disorders including AMD Wu et al, 2020;Xiong et al, 2021;Yang et al, 2021;ElShelmani et al, 2021a;Acuña et al, 2022). This suggests that their presence in circulation reflects early changes in retinal homeostasis and we hypothesize that these miRNAs have the potential to be early indicators of disease onset.…”

Section: Circulating Mirnas Are Linked To Photoreceptor Degenerationmentioning

confidence: 91%

Serum miRNA modulations indicate changes in retinal morphology

Aggio-Bruce

Schümann

Cioanca

et al. 2023

Front. Mol. Neurosci.

View full text Add to dashboard Cite

BackgroundAge-related macular degeneration (AMD) is the leading cause of vision loss in the developed world and the detection of its onset and progression are based on retinal morphological assessments. MicroRNA (miRNA) have been explored extensively as biomarkers for a range of neurological diseases including AMD, however differences in experimental design and the complexity of human biology have resulted in little overlap between studies. Using preclinical animal models and clinical samples, this study employs a novel approach to determine a serum signature of AMD progression.MethodsSerum miRNAs were extracted from mice exposed to photo-oxidative damage (PD; 0, 1, 3 and 5 days), and clinical samples from patients diagnosed with reticular pseudodrusen or atrophic AMD. The expression of ~800 miRNAs was measured using OpenArray™, and differential abundance from controls was determined using the HTqPCR R package followed by pathway analysis with DAVID. MiRNA expression changes were compared against quantifiable retinal histological indicators. Finally, the overlap of miRNA changes observed in the mouse model and human patient samples was investigated.ResultsDifferential miRNA abundance was identified at all PD time-points and in clinical samples. Importantly, these were associated with inflammatory pathways and histological changes in the retina. Further, we were able to align findings in the mouse serum to those of clinical patients.ConclusionIn conclusion, serum miRNAs are a valid tool as diagnostics for the early detection of retinal degeneration, as they reflect key changes in retinal health. The combination of pre-clinical animal models and human patient samples led to the identification of a preliminary serum miRNA signature for AMD. This study is an important platform for the future development of a diagnostic serum miRNA panel for the early detection of retinal degeneration.

show abstract

miR-294 and miR-410 Negatively Regulate Tnfa, Arginine Transporter Cat1/2, and Nos2 mRNAs in Murine Macrophages Infected with Leishmania amazonensis

Cited by 6 publications

References 61 publications

Polyamines shift expression of macrophage L-arginine metabolism related-genes during Leishmania amazonensis infection

Polyamines shift expression of macrophage L-arginine metabolism related-genes during Leishmania amazonensis infection

Putrescine supplementation shifts macrophage L-arginine metabolism related-genes reducing Leishmania amazonensis infection

Serum miRNA modulations indicate changes in retinal morphology

Contact Info

Product

Resources

About