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10.1371/journal.ppat.1006367 http://scihub22266oqcxt.onion/10.1371/journal.ppat.1006367 C5453634!5453634 !28570642     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\28570642 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       PLoS+Pathog 2017 ; 13 (6 ): e1006367 Nephropedia Template TP {{tp|p=28570642 |t=2017. Mycobacterium tuberculosis subverts negative regulatory pathways in human macrophages to drive immunopathology |pdf=|usr=}}{{28570642 }} gab.com Text Mycobacterium tuberculosis subverts negative regulatory pathways in human macrophages to drive immunopathology JO: PLoS Pathog http://www.kidney.de/pget.php?&tw=1&pmid=28570642 #FOAvip Tuberculosis remains a global pandemic and drives lung matrix destruction to transmit. Whilst pathways driving inflammatory responses in macrophages have been relatively well described, negative regulatory pathways are less well defined. We hypothesised that Mycobacterium tuberculosis (Mtb) specifically targets negative regulatory pathways to augment immunopathology. Inhibition of signalling through the PI3K/AKT/mTORC1 pathway increased matrix metalloproteinase-1 (MMP-1) gene expression and secretion, a collagenase central to TB pathogenesis, and multiple pro-inflammatory cytokines. In patients with confirmed pulmonary TB, PI3K? expression was absent within granulomas. Furthermore, Mtb infection suppressed PI3K? gene expression in macrophages. Interestingly, inhibition of the MNK pathway, downstream of pro-inflammatory p38 and ERK MAPKs, also increased MMP-1 secretion, whilst suppressing secretion of TH1 cytokines. Cross-talk between the PI3K and MNK pathways was demonstrated at the level of eIF4E phosphorylation. Mtb globally suppressed the MMP-inhibitory pathways in macrophages, reducing levels of mRNAs encoding PI3K?, mTORC-1 and MNK-1 via upregulation of miRNAs. Therefore, Mtb disrupts negative regulatory pathways at multiple levels in macrophages to drive a tissue-destructive phenotype that facilitates transmission. Twit Text FOAVip Mycobacterium tuberculosis subverts negative regulatory pathways in human macrophages to drive immunopathology ????PLoS Pathog http://www.kidney.de/pget.php?&tw=1&pmid=28570642 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28570642 #FOAvip English Wikipedia <ref>{{Cite pmid|28570642 }}</ref> Mycobacterium tuberculosis subverts negative regulatory pathways in human macrophages to drive immunopathology #MMPMID28570642 Brace PT ; Tezera LB ; Bielecka MK ; Mellows T ; Garay D ; Tian S ; Rand L ; Green J ; Jogai S ; Steele AJ ; Millar TM ; Sanchez-Elsner T ; Friedland JS ; Proud CG ; Elkington PT PLoS Pathog 2017[Jun]; 13 (6 ): e1006367 PMID28570642 show ga Tuberculosis remains a global pandemic and drives lung matrix destruction to transmit. Whilst pathways driving inflammatory responses in macrophages have been relatively well described, negative regulatory pathways are less well defined. We hypothesised that Mycobacterium tuberculosis (Mtb) specifically targets negative regulatory pathways to augment immunopathology. Inhibition of signalling through the PI3K/AKT/mTORC1 pathway increased matrix metalloproteinase-1 (MMP-1) gene expression and secretion, a collagenase central to TB pathogenesis, and multiple pro-inflammatory cytokines. In patients with confirmed pulmonary TB, PI3K? expression was absent within granulomas. Furthermore, Mtb infection suppressed PI3K? gene expression in macrophages. Interestingly, inhibition of the MNK pathway, downstream of pro-inflammatory p38 and ERK MAPKs, also increased MMP-1 secretion, whilst suppressing secretion of TH1 cytokines. Cross-talk between the PI3K and MNK pathways was demonstrated at the level of eIF4E phosphorylation. Mtb globally suppressed the MMP-inhibitory pathways in macrophages, reducing levels of mRNAs encoding PI3K?, mTORC-1 and MNK-1 via upregulation of miRNAs. Therefore, Mtb disrupts negative regulatory pathways at multiple levels in macrophages to drive a tissue-destructive phenotype that facilitates transmission. |Animals [MESH] |Humans [MESH] |Macrophages/*immunology/microbiology [MESH] |Matrix Metalloproteinase 1/genetics/immunology [MESH] |Mechanistic Target of Rapamycin Complex 1 [MESH] |Mice [MESH] |Multiprotein Complexes/genetics/immunology [MESH] |Mycobacterium tuberculosis/genetics/*immunology/physiology [MESH] |Phosphatidylinositol 3-Kinases/genetics/immunology [MESH] |TOR Serine-Threonine Kinases/genetics/immunology [MESH]Mycobacterium tuberculosis subverts negative regulatory pathways in hu(epmc).pdf DeepDyve Pubget Overpricing