Effects of acute ethanol exposure on cytokine production by primary airway smooth muscle cells

Lata Kaphalia, Mridul Kalita, Bhupendra Kaphalia, William Calhoun

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Both chronic and binge alcohol abuse can be significant risk factors for inflammatory lung diseases such as acute respiratory distress syndrome and chronic obstructive pulmonary disease. However, metabolic basis of alcohol-related lung disease is not well defined, and may include key metabolites of ethanol [EtOH] in addition to EtOH itself. Therefore, we investigated the effects of EtOH, acetaldehyde [ACE], and fatty acid ethyl esters [FAEEs] on oxidative stress, endoplasmic reticulum (ER) stress, AMP-activated protein kinase (AMPK) signaling and nuclear translocation of phosphorylated (p)-NF-κB p65 in primary human airway smooth muscle (HASM) cells stimulated to produce cytokines using LPS exposure. Both FAEEs and ACE induced evidence of cellular oxidative stress and ER stress, and increased p-NF-κB in nuclear extracts. EtOH and its metabolites decreased p-AMPKα activation, and induced expression of fatty acid synthase, and decreased expression of sirtuin 1. In general, EtOH decreased secretion of IP-10, IL-6, eotaxin, GCSF, and MCP-1. However, FAEEs and ACE increased these cytokines, suggesting that both FAEEs and ACE as compared to EtOH itself are proinflammatory. A direct effect of EtOH could be consistent with blunted immune response. Collectively, these two features of EtOH exposure, coupled with the known inhibition of innate immune response in our model might explain some clinical manifestations of EtOH exposure in the lung.

Original languageEnglish (US)
Pages (from-to)85-93
Number of pages9
JournalToxicology and Applied Pharmacology
Volume292
DOIs
StatePublished - Feb 1 2016

Fingerprint

Acetaldehyde
Pulmonary diseases
Smooth Muscle Myocytes
Muscle
Esters
Ethanol
Fatty Acids
Cells
Cytokines
AMP-Activated Protein Kinases
Endoplasmic Reticulum Stress
Oxidative stress
Metabolites
Lung Diseases
Oxidative Stress
Sirtuin 1
Alcohols
Fatty Acid Synthases
Adult Respiratory Distress Syndrome
Innate Immunity

Keywords

  • Acetaldehyde
  • AMPK signaling
  • Cytokines
  • Ethanol
  • Fatty acid ethyl esters
  • Human airway smooth muscle cells

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Effects of acute ethanol exposure on cytokine production by primary airway smooth muscle cells. / Kaphalia, Lata; Kalita, Mridul; Kaphalia, Bhupendra; Calhoun, William.

In: Toxicology and Applied Pharmacology, Vol. 292, 01.02.2016, p. 85-93.

Research output: Contribution to journalArticle

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