Elevated cyclic AMP inhibits mycobacterium tuberculosis-stimulated T-cell IFN-γ secretion through type I protein kinase A
Cyclic adenosine monophosphate (cAMP) is critical in immune regulation, and its role in tuberculosis infection remains unclear. We determined the levels of cAMP in peripheral blood mononuclear cells (PBMC) from tuberculosis patients and the mechanisms for cAMP suppression of IFN-γ production. PBMC f...
Guardado en:
| Publicado: |
2018
|
|---|---|
| Materias: | |
| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00221899_v217_n11_p1821_Chung http://hdl.handle.net/20.500.12110/paper_00221899_v217_n11_p1821_Chung |
| Aporte de: |
| id |
paper:paper_00221899_v217_n11_p1821_Chung |
|---|---|
| record_format |
dspace |
| spelling |
paper:paper_00221899_v217_n11_p1821_Chung2023-06-08T14:47:02Z Elevated cyclic AMP inhibits mycobacterium tuberculosis-stimulated T-cell IFN-γ secretion through type I protein kinase A Cyclic adenosine monophosphate Cytokine Human Transcription factor Tuberculosis activating transcription factor 2 cyclic AMP cyclic AMP dependent protein kinase 1 cyclic AMP responsive element binding protein gamma interferon interleukin 10 interleukin 12 microRNA 155 protein c jun transforming growth factor beta1 Article controlled study cytokine production cytokine release gel mobility shift assay gene expression human human cell latent tuberculosis lung tuberculosis major clinical study Mycobacterium tuberculosis nonhuman peripheral blood mononuclear cell priority journal protein expression Western blotting Cyclic adenosine monophosphate (cAMP) is critical in immune regulation, and its role in tuberculosis infection remains unclear. We determined the levels of cAMP in peripheral blood mononuclear cells (PBMC) from tuberculosis patients and the mechanisms for cAMP suppression of IFN-γ production. PBMC from tuberculosis patients contained significantly elevated cAMP than latent tuberculosis infected subjects (LTBI), with an inverse correlation with IFN-γ production. Consistent with this, the expression of cAMP response element binding protein (CREB), activating transcription factor (ATF)-2 and c-Jun were reduced in tuberculosis patients compared with LTBI. PKA type I specific cAMP analogs inhibited Mtb-stimulated IFN-g production by PBMC through suppression of Mtb-induced IFN-γ promoter binding activities of CREB, ATF-2, and c-Jun and also miR155, the target miRNA of these transcription factors. Neutralizing both IL-10 and TGF-β1 or supplementation of IL-12 restored cAMP-suppressed IFN-g production. We conclude that increased cAMP inhibits IFN-g production through PKA type I pathway in tuberculosis infection. © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. 2018 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00221899_v217_n11_p1821_Chung http://hdl.handle.net/20.500.12110/paper_00221899_v217_n11_p1821_Chung |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Cyclic adenosine monophosphate Cytokine Human Transcription factor Tuberculosis activating transcription factor 2 cyclic AMP cyclic AMP dependent protein kinase 1 cyclic AMP responsive element binding protein gamma interferon interleukin 10 interleukin 12 microRNA 155 protein c jun transforming growth factor beta1 Article controlled study cytokine production cytokine release gel mobility shift assay gene expression human human cell latent tuberculosis lung tuberculosis major clinical study Mycobacterium tuberculosis nonhuman peripheral blood mononuclear cell priority journal protein expression Western blotting |
| spellingShingle |
Cyclic adenosine monophosphate Cytokine Human Transcription factor Tuberculosis activating transcription factor 2 cyclic AMP cyclic AMP dependent protein kinase 1 cyclic AMP responsive element binding protein gamma interferon interleukin 10 interleukin 12 microRNA 155 protein c jun transforming growth factor beta1 Article controlled study cytokine production cytokine release gel mobility shift assay gene expression human human cell latent tuberculosis lung tuberculosis major clinical study Mycobacterium tuberculosis nonhuman peripheral blood mononuclear cell priority journal protein expression Western blotting Elevated cyclic AMP inhibits mycobacterium tuberculosis-stimulated T-cell IFN-γ secretion through type I protein kinase A |
| topic_facet |
Cyclic adenosine monophosphate Cytokine Human Transcription factor Tuberculosis activating transcription factor 2 cyclic AMP cyclic AMP dependent protein kinase 1 cyclic AMP responsive element binding protein gamma interferon interleukin 10 interleukin 12 microRNA 155 protein c jun transforming growth factor beta1 Article controlled study cytokine production cytokine release gel mobility shift assay gene expression human human cell latent tuberculosis lung tuberculosis major clinical study Mycobacterium tuberculosis nonhuman peripheral blood mononuclear cell priority journal protein expression Western blotting |
| description |
Cyclic adenosine monophosphate (cAMP) is critical in immune regulation, and its role in tuberculosis infection remains unclear. We determined the levels of cAMP in peripheral blood mononuclear cells (PBMC) from tuberculosis patients and the mechanisms for cAMP suppression of IFN-γ production. PBMC from tuberculosis patients contained significantly elevated cAMP than latent tuberculosis infected subjects (LTBI), with an inverse correlation with IFN-γ production. Consistent with this, the expression of cAMP response element binding protein (CREB), activating transcription factor (ATF)-2 and c-Jun were reduced in tuberculosis patients compared with LTBI. PKA type I specific cAMP analogs inhibited Mtb-stimulated IFN-g production by PBMC through suppression of Mtb-induced IFN-γ promoter binding activities of CREB, ATF-2, and c-Jun and also miR155, the target miRNA of these transcription factors. Neutralizing both IL-10 and TGF-β1 or supplementation of IL-12 restored cAMP-suppressed IFN-g production. We conclude that increased cAMP inhibits IFN-g production through PKA type I pathway in tuberculosis infection. © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. |
| title |
Elevated cyclic AMP inhibits mycobacterium tuberculosis-stimulated T-cell IFN-γ secretion through type I protein kinase A |
| title_short |
Elevated cyclic AMP inhibits mycobacterium tuberculosis-stimulated T-cell IFN-γ secretion through type I protein kinase A |
| title_full |
Elevated cyclic AMP inhibits mycobacterium tuberculosis-stimulated T-cell IFN-γ secretion through type I protein kinase A |
| title_fullStr |
Elevated cyclic AMP inhibits mycobacterium tuberculosis-stimulated T-cell IFN-γ secretion through type I protein kinase A |
| title_full_unstemmed |
Elevated cyclic AMP inhibits mycobacterium tuberculosis-stimulated T-cell IFN-γ secretion through type I protein kinase A |
| title_sort |
elevated cyclic amp inhibits mycobacterium tuberculosis-stimulated t-cell ifn-γ secretion through type i protein kinase a |
| publishDate |
2018 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00221899_v217_n11_p1821_Chung http://hdl.handle.net/20.500.12110/paper_00221899_v217_n11_p1821_Chung |
| _version_ |
1768542926252539904 |