Introduction: Vitamin D has been recognized to play an important role in human immune system and function. In the pulmonary system, vitamin D regulates the function of anti-microbial peptides such as Cathelicidin/LL-37. Human Cathelicidin/LL-37 is a bactericidal, bacteriostatic and antiviral endogenous peptide with protective immune functions. Chronic exposure to excessive alcohol has the potential to reduce the levels of vitamin D (active and inactive) and in turn result in down-regulation of Cathelicidin/LL-37. Alcohol-mediated reduction of LL-37 maybe partly responsible for increased incidence of more frequent and severe respiratory infections among subjects with Alcohol Use Disorder (AUD).
The objective of this project was to investigate the mechanism by which alcohol exerts its influence on vitamin D metabolism and consequently (based on the observed influence) establish the relationships between chronic ethanol exposure, levels of pulmonary vitamin D and Cathelicidin/LL-37.
Materials and Methods: Human Pulmonary Alveolar/Bronchial Epithelial cell lines were grown and cultured. The cultured cells were treated with ethanol and Diallyl Disulfide (DADS). In addition, Broncho Alveolar Lavage Fluid (BALF) samples of AUD subjects and healthy controls were obtained from CoPARC (Colorado Pulmonary Alcohol Research Consortium (Denver and Atlanta Centers). Following exposure, we quantified total protein levels of vitamin D, phase one metabolizing enzymes (CYP450) and LL-37 in the cell lines and BALF. DADS has been found to have inhibitory effects on ethanol metabolic pathway mediated by CYP2E1, an enzyme that catabolize alcohol into its toxic metabolites through oxidation reaction. Study participants (AUD subjects and healthy controls) were recruited and screened using Alcohol Use Disorder Identification Test (AUDIT) score and a standardized questionnaire.
Results: The levels of 25(OH)D3, 1,25(OH)2D3, Cathelicidin/LL-37, CYP27B1 proteins were significantly reduced (p < 0.05) when compared with control group (cell lines). Whereas, the level of CYP2E1 and CYP24A1 were significantly elevated following exposure to ethanol (p < 0.05), when compared to the control group. Similar trends were observed in the BALF samples when the levels of the above proteins were quantified, compared to matched healthy controls. However, upon exposure to DADS, a reversal of the above trends was observed in the quantification of respective total proteins.
Conclusion: Chronic exposure to alcohol has the potential to reduce levels of pulmonary vitamin D which in turn may result in down-regulation and/or in-activation of anti-microbial peptides, LL-37, a protein which play significant protective immune functions in the human pulmonary system.
|Commitee:||Lichtveld, Maureen, Wickliffe, Jeffrey|
|School:||Tulane University, School of Public Health and Tropical Medicine|
|Department:||Global Environmental Health Sciences (GEHS)|
|School Location:||United States -- Louisiana|
|Source:||DAI-B 81/4(E), Dissertation Abstracts International|
|Subjects:||Toxicology, Public health|
|Keywords:||Alcohol, Alveolar, Anti-microbial-peptides, Cathelicidin, Pulmonary, Vitamin D|
Copyright in each Dissertation and Thesis is retained by the author. All Rights Reserved
The supplemental file or files you are about to download were provided to ProQuest by the author as part of a
dissertation or thesis. The supplemental files are provided "AS IS" without warranty. ProQuest is not responsible for the
content, format or impact on the supplemental file(s) on our system. in some cases, the file type may be unknown or
may be a .exe file. We recommend caution as you open such files.
Copyright of the original materials contained in the supplemental file is retained by the author and your access to the
supplemental files is subject to the ProQuest Terms and Conditions of use.
Depending on the size of the file(s) you are downloading, the system may take some time to download them. Please be