In:
Alcoholism: Clinical and Experimental Research, Wiley, Vol. 39, No. 9 ( 2015-09), p. 1691-1697
Abstract:
The lung has a highly regulated system of innate immunity to protect itself from inhaled microbes and toxins. The first line of defense is mucociliary clearance, but if invaders overcome this, inflammatory pathways are activated. Toll‐like receptors ( TLR s) are expressed on the airway epithelium. Their signaling initiates the inflammatory cascade and leads to production of inflammatory cytokines such as interleukin (IL) ‐6 and IL ‐8. We hypothesized that airway epithelial insults, including heavy alcohol intake or smoking, would alter the expression of TLR s on the airway epithelium. Methods Bronchoscopy with bronchoalveolar lavage and brushings of the airway epithelium was performed in otherwise healthy subjects who had normal chest radiographs and spirometry. A history of alcohol use disorders ( AUD s) was ascertained using the Alcohol Use Disorders Identification Test ( AUDIT ), and a history of cigarette smoking was also obtained. Age, gender, and nutritional status in all groups were similar. We used real‐time polymerase chain reaction (PCR) to quantitate TLR1 to 9 and enzyme‐linked immune assay to measure tumor necrosis factor‐ α , IL ‐6, and IL ‐8. Results Airway brushings were obtained from 26 nonsmoking/non‐ AUD subjects, 28 smoking/non‐ AUD subjects, 36 smoking/ AUD subjects, and 17 nonsmoking/ AUD subjects. We found that TLR 2 is up‐regulated in AUD subjects, compared to nonsmoking/non‐ AUD subjects, and correlated with their AUDIT scores. We also measured a decrease in TLR 4 expression in AUD subjects that correlated with AUDIT score. IL ‐6 and IL ‐8 were also increased in bronchial washings from AUD subjects. Conclusions We have previously demonstrated in normal human bronchial epithelial cells that in vitro alcohol exposure up‐regulates TLR 2 through a NO / cGMP / PKG ‐dependent pathway, resulting in up‐regulation of inflammatory cytokine production after Gram‐positive bacterial product stimulation. Our current translational study confirms that TLR 2 is also up‐regulated in humans with AUD s.
Type of Medium:
Online Resource
ISSN:
0145-6008
,
1530-0277
DOI:
10.1111/acer.2015.39.issue-9
Language:
English
Publisher:
Wiley
Publication Date:
2015
detail.hit.zdb_id:
2046886-6
detail.hit.zdb_id:
3167872-5
SSG:
15,3
Permalink