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HIV Tat Protein and TGF-β Suppresses CFTR Biogenesis and Activity by Microrna Mediated Gene Silencing
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A7116 - HIV Tat Protein and TGF-β Suppresses CFTR Biogenesis and Activity by Microrna Mediated Gene Silencing
Author Block: R. K. Dutta1, S. Chinnapaiyan2, M. Nair1, H. J. Unwalla1; 1Immunology, Florida International University, Miami, FL, United States, 2Florida International University, Miami, FL, United States.
Background: Complications in respiratory system are common in HIV patients, specifically in HIV-infected patients who smoke. HIV infected person who smoke are six times more likely to get infected with pneumonia with higher mortality rate as compared with non-infected age controls. Obstructive lung diseases like COPD, pulmonary hypertension, and pneumonia are the prominent factor for morbidity and mortality despite of having combination antiretroviral therapy (cART). Tobacco smoke and HIV infection was identified as pivotal causes to suppress nasal mucociliary clearance (MCC) as well as bronchial MCC, primary innate defense mechanism in airway system.
Methods: All experiments were performed with primary human bronchial epithelial cells, re-differentiated at the air-liquid interface (ALI). NHBE ALI cultures were exposed to whole cigarette smoke (CS) using a SCIREQ inExpose smoke robot At the end of experiments, cells were lysed and total RNA was extracted and analyzed to quantify CFTR mRNA. Ussing chamber experiemnts were performed to determine CFTR function in NHBE ALI cultures exposed to ciagarette smoke and/or TGF-beta
Results: Our study showed that TGF-beta signaling is enhanced by HIV Tat protein and cigarette smoke. We found that HIV Tat protein and cigarette smoke inhibit CFTR biogenesis and activity in normal human bronchial epithelial (NHBE) cells via a common TGF-β signaling pathway. Chromatin immunoprecipitation with RNA Polymerase II demonstrated that transcription from the CFTR promoter is unaffected and blocking the miRNA processing pathway with Aurin Tricarboxylic acid (ATA) restore CFTR inhibition caused by TGF- β. MicroRNA array result concluded that several microRNAs are induced by HIV Tat protein and TGF-beta capable of targeting CFTR.
Conclusions-Implicaions: HIV Tat and cigarette smoke suppress CFTR biogenesis and function via TGF-beta signaling
Author Block: R. K. Dutta1, S. Chinnapaiyan2, M. Nair1, H. J. Unwalla1; 1Immunology, Florida International University, Miami, FL, United States, 2Florida International University, Miami, FL, United States.
Background: Complications in respiratory system are common in HIV patients, specifically in HIV-infected patients who smoke. HIV infected person who smoke are six times more likely to get infected with pneumonia with higher mortality rate as compared with non-infected age controls. Obstructive lung diseases like COPD, pulmonary hypertension, and pneumonia are the prominent factor for morbidity and mortality despite of having combination antiretroviral therapy (cART). Tobacco smoke and HIV infection was identified as pivotal causes to suppress nasal mucociliary clearance (MCC) as well as bronchial MCC, primary innate defense mechanism in airway system.
Methods: All experiments were performed with primary human bronchial epithelial cells, re-differentiated at the air-liquid interface (ALI). NHBE ALI cultures were exposed to whole cigarette smoke (CS) using a SCIREQ inExpose smoke robot At the end of experiments, cells were lysed and total RNA was extracted and analyzed to quantify CFTR mRNA. Ussing chamber experiemnts were performed to determine CFTR function in NHBE ALI cultures exposed to ciagarette smoke and/or TGF-beta
Results: Our study showed that TGF-beta signaling is enhanced by HIV Tat protein and cigarette smoke. We found that HIV Tat protein and cigarette smoke inhibit CFTR biogenesis and activity in normal human bronchial epithelial (NHBE) cells via a common TGF-β signaling pathway. Chromatin immunoprecipitation with RNA Polymerase II demonstrated that transcription from the CFTR promoter is unaffected and blocking the miRNA processing pathway with Aurin Tricarboxylic acid (ATA) restore CFTR inhibition caused by TGF- β. MicroRNA array result concluded that several microRNAs are induced by HIV Tat protein and TGF-beta capable of targeting CFTR.
Conclusions-Implicaions: HIV Tat and cigarette smoke suppress CFTR biogenesis and function via TGF-beta signaling
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