miR-294 and miR-410 Negatively Regulate <i>Tnfa</i>, Arginine Transporter <i>Cat</i>1/2, and <i>Nos</i>2 mRNAs in Murine Macrophages Infected with <i>Leishmania amazonensis</i>
MicroRNAs are small non-coding RNAs that regulate cellular processes by the post-transcriptional regulation of gene expression, including immune responses. The shift in the miRNA profiling of murine macrophages infected with <i>Leishmania amazonensis</i> can change inflammatory response...
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MDPI AG
2022-02-01
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| Series: | Non-Coding RNA |
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| Online Access: | https://www.mdpi.com/2311-553X/8/1/17 |
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| author | Stephanie Maia Acuña Jonathan Miguel Zanatta Camilla de Almeida Bento Lucile Maria Floeter-Winter Sandra Marcia Muxel |
| author_facet | Stephanie Maia Acuña Jonathan Miguel Zanatta Camilla de Almeida Bento Lucile Maria Floeter-Winter Sandra Marcia Muxel |
| author_sort | Stephanie Maia Acuña |
| collection | DOAJ |
| description | MicroRNAs are small non-coding RNAs that regulate cellular processes by the post-transcriptional regulation of gene expression, including immune responses. The shift in the miRNA profiling of murine macrophages infected with <i>Leishmania amazonensis</i> can change inflammatory response and metabolism. L-arginine availability and its conversion into nitric oxide by nitric oxide synthase 2 (<i>Nos</i>2) or ornithine (a polyamine precursor) by arginase 1/2 regulate macrophage microbicidal activity. This work aimed to evaluate the function of miR-294, miR-301b, and miR-410 during early C57BL/6 bone marrow-derived macrophage infection with <i>L. amazonensis</i>. We observed an upregulation of miR-294 and miR-410 at 4 h of infection, but the levels of miR-301b were not modified. This profile was not observed in LPS-stimulated macrophages. We also observed decreased levels of those miRNAs target genes during infection, such as Cationic amino acid transporters 1 (<i>Cat</i>1/<i>Slc</i>7<i>a</i>1), <i>Cat</i>2<i>/Slc</i>7<i>a</i>22 and <i>Nos</i>2; genes were upregulated in LPS stimuli. The functional inhibition of miR-294 led to the upregulation of <i>Cat</i>2 and <i>Tnfa</i> and the dysregulation of <i>Nos</i>2, while miR-410 increased <i>Cat</i>1 levels. miR-294 inhibition reduced the number of amastigotes per infected macrophage, showing a reduction in the parasite growth inside the macrophage. These data identified miR-294 and miR-410 biomarkers for a potential regulator in the inflammatory profiles of microphages mediated by <i>L. amazonensis</i> infection. This research provides novel insights into immune dysfunction contributing to infection outcomes and suggests the use of the antagomiRs/inhibitors of miR-294 and miR-410 as new therapeutic strategies to modulate inflammation and to decrease parasitism. |
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| institution | Directory Open Access Journal |
| issn | 2311-553X |
| language | English |
| last_indexed | 2024-03-09T21:18:31Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
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| series | Non-Coding RNA |
| spelling | doaj.art-124029b4cc14476e9446bb954ee6ce712023-11-23T21:27:21ZengMDPI AGNon-Coding RNA2311-553X2022-02-01811710.3390/ncrna8010017miR-294 and miR-410 Negatively Regulate <i>Tnfa</i>, Arginine Transporter <i>Cat</i>1/2, and <i>Nos</i>2 mRNAs in Murine Macrophages Infected with <i>Leishmania amazonensis</i>Stephanie Maia Acuña0Jonathan Miguel Zanatta1Camilla de Almeida Bento2Lucile Maria Floeter-Winter3Sandra Marcia Muxel4Departamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo, São Paulo 05508-090, SP, BrazilDepartamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo, São Paulo 05508-090, SP, BrazilDepartamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo, São Paulo 05508-090, SP, BrazilDepartamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo, São Paulo 05508-090, SP, BrazilDepartamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo, São Paulo 05508-090, SP, BrazilMicroRNAs are small non-coding RNAs that regulate cellular processes by the post-transcriptional regulation of gene expression, including immune responses. The shift in the miRNA profiling of murine macrophages infected with <i>Leishmania amazonensis</i> can change inflammatory response and metabolism. L-arginine availability and its conversion into nitric oxide by nitric oxide synthase 2 (<i>Nos</i>2) or ornithine (a polyamine precursor) by arginase 1/2 regulate macrophage microbicidal activity. This work aimed to evaluate the function of miR-294, miR-301b, and miR-410 during early C57BL/6 bone marrow-derived macrophage infection with <i>L. amazonensis</i>. We observed an upregulation of miR-294 and miR-410 at 4 h of infection, but the levels of miR-301b were not modified. This profile was not observed in LPS-stimulated macrophages. We also observed decreased levels of those miRNAs target genes during infection, such as Cationic amino acid transporters 1 (<i>Cat</i>1/<i>Slc</i>7<i>a</i>1), <i>Cat</i>2<i>/Slc</i>7<i>a</i>22 and <i>Nos</i>2; genes were upregulated in LPS stimuli. The functional inhibition of miR-294 led to the upregulation of <i>Cat</i>2 and <i>Tnfa</i> and the dysregulation of <i>Nos</i>2, while miR-410 increased <i>Cat</i>1 levels. miR-294 inhibition reduced the number of amastigotes per infected macrophage, showing a reduction in the parasite growth inside the macrophage. These data identified miR-294 and miR-410 biomarkers for a potential regulator in the inflammatory profiles of microphages mediated by <i>L. amazonensis</i> infection. This research provides novel insights into immune dysfunction contributing to infection outcomes and suggests the use of the antagomiRs/inhibitors of miR-294 and miR-410 as new therapeutic strategies to modulate inflammation and to decrease parasitism.https://www.mdpi.com/2311-553X/8/1/17microRNAmacrophage<i>Leishmania</i>nitric oxide synthase 2<i>Cat</i>2<i>/Slc</i>7<i>a</i>2<i>Tnfa</i> |
| spellingShingle | Stephanie Maia Acuña Jonathan Miguel Zanatta Camilla de Almeida Bento Lucile Maria Floeter-Winter Sandra Marcia Muxel miR-294 and miR-410 Negatively Regulate <i>Tnfa</i>, Arginine Transporter <i>Cat</i>1/2, and <i>Nos</i>2 mRNAs in Murine Macrophages Infected with <i>Leishmania amazonensis</i> Non-Coding RNA microRNA macrophage <i>Leishmania</i> nitric oxide synthase 2 <i>Cat</i>2<i>/Slc</i>7<i>a</i>2 <i>Tnfa</i> |
| title | miR-294 and miR-410 Negatively Regulate <i>Tnfa</i>, Arginine Transporter <i>Cat</i>1/2, and <i>Nos</i>2 mRNAs in Murine Macrophages Infected with <i>Leishmania amazonensis</i> |
| title_full | miR-294 and miR-410 Negatively Regulate <i>Tnfa</i>, Arginine Transporter <i>Cat</i>1/2, and <i>Nos</i>2 mRNAs in Murine Macrophages Infected with <i>Leishmania amazonensis</i> |
| title_fullStr | miR-294 and miR-410 Negatively Regulate <i>Tnfa</i>, Arginine Transporter <i>Cat</i>1/2, and <i>Nos</i>2 mRNAs in Murine Macrophages Infected with <i>Leishmania amazonensis</i> |
| title_full_unstemmed | miR-294 and miR-410 Negatively Regulate <i>Tnfa</i>, Arginine Transporter <i>Cat</i>1/2, and <i>Nos</i>2 mRNAs in Murine Macrophages Infected with <i>Leishmania amazonensis</i> |
| title_short | miR-294 and miR-410 Negatively Regulate <i>Tnfa</i>, Arginine Transporter <i>Cat</i>1/2, and <i>Nos</i>2 mRNAs in Murine Macrophages Infected with <i>Leishmania amazonensis</i> |
| title_sort | mir 294 and mir 410 negatively regulate i tnfa i arginine transporter i cat i 1 2 and i nos i 2 mrnas in murine macrophages infected with i leishmania amazonensis i |
| topic | microRNA macrophage <i>Leishmania</i> nitric oxide synthase 2 <i>Cat</i>2<i>/Slc</i>7<i>a</i>2 <i>Tnfa</i> |
| url | https://www.mdpi.com/2311-553X/8/1/17 |
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