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Ethanol-mediated dysregulation of cytokines and human anti-microbial peptide cathelicidin / Ethanol consumption is known to increase the prevalence and severity of respiratory infection and impaired immunity. The relationships between ethanol exposure, vitamin D levels, the anti-microbial protein cathelicidin/LL-37, other chemokines and cytokines, and their roles in pulmonary infections are explored in this report. Information from experimental model systems that included pulmonary cell culture, mice, and primates were compared to data from humans with alcohol use disorder (AUD) and normal controls. Cathelicidin/LL-37 levels were reduced by ethanol exposure of Nuli-1 airway epithelial cells, which is consistent with the model of enhanced airway sensitivity to infection. The vitamin D receptor positively regulates cathelicidin/LL-37 levels. A reduction in the circulating vitamin D in the Rhesus monkey model following ethanol exposure that may impact cathelicidin/LL-37 expression. Serum samples from ethanol exposed mice, Rhesus monkeys and humans with AUD showed variable expression patterns with respect to cytokines and chemokine, some of which may relate to changes in immunity and infection sensitivity. Protein microarrays revealed altered inflammatory biomarkers in the ethanol-exposed population with AUD. Principle component analysis-derived clustering methodology signaled the presence of systemic inflammation in AUD subjects. The combination of immunological impairment and persistent inflammatory biomarkers are consistent with the known predisposition of individuals with AUD to the development of respiratory infections and acute respiratory distress syndrome. / 1 / Phanuwat Sriyotha

  1. tulane:120547
Date January 2020
ContributorsSriyotha, Phanuwat (author), Shankar, Arti (Thesis advisor), School of Public Health & Tropical Medicine Global Environmental Health Sciences (Degree granting institution)
PublisherTulane University
Source SetsTulane University
Detected LanguageEnglish
Formatelectronic, pages:  83
RightsNo embargo, Copyright is in accordance with U.S. Copyright law.

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