Malondialdehyde-acetaldehyde-adducted bovine serum albumin activates protein kinase C and stimulates interleukin-8 release in bovine bronchial epithelial cells.
Previous study results have demonstrated that cigarette smoke or acetaldehyde rapidly stimulates protein kinase C (PKC)-mediated release of interleukin-8 (IL-8) in bovine bronchial epithelial cells (BECs). Low concentrations of acetaldehyde combine synergistically with malondialdehyde to increase significantly maximal BEC PKC activity at 48 to 96 h stimulation. Because more than 95% of alcoholics are cigarette smokers, we hypothesized that malondialdehyde, an inflammation product of lipid peroxidation, and acetaldehyde, both a product of ethanol metabolism and a component of cigarette smoke, might stimulate PKC-mediated IL-8 release in BECs by malondialdehyde-acetaldehyde (MAA) adduct formation, rather than as free aldehydes. Protein kinase C activity is maximally elevated in BECs treated with 50 microg/ml of BSA-MAA from approximately 1 to 3 h. This activity subsequently begins to decrease by 4 to 6 h, with a return to baseline unstimulated kinase activity levels by 24 h. No activation of cyclic AMP-dependent protein kinase (PKA) or cyclic GMP-dependent protein kinase (PKG) was observed in BSA-MAA-treated BECs. The MAA adduct activation of PKC was followed by a fourfold to tenfold greater release of IL-8 over that observed for both BECs exposed to media only and BSA control-treated BECs. Protein kinase C activation and IL-8 release were blocked by pretreating BECs with 1 microM calphostin C or 100 nM of the PKC alpha-specific inhibitor, Go 6976. Isoform-specific inhibitors to PKC beta, PKC delta, and PKC zeta failed to inhibit completely MAA adduct-stimulated PKC or IL-8 release. Results of these studies indicate that metabolites derived from ethanol and cigarette smoke, such as acetaldehyde and malondialdehyde, form adducts that stimulate airway epithelial cell PKC alpha-mediated release of promigratory cytokines.
Wyatt
T A
TA
Research Service, Department of Veterans Affairs Medical Center, 4101 Woolworth Avenue, Omaha, NE 68105, USA. twyatt@unmc.edu
Kharbanda
K K
KK
Tuma
D J
DJ
Sisson
J H
JH
D000079:Acetaldehyde / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D020536:Enzyme Activators / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D008315:Malondialdehyde / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051571:Protein Kinase C-alpha; D012710:Serum Albumin, Bovine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D012907:Smoking / Q000378:metabolism
D020536:Enzyme Activators; D016209:Interleukin-8; D007527:Isoenzymes; D012710:Serum Albumin, Bovine; D008315:Malondialdehyde; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D000079:Acetaldehyde