Differential activation of NF kappa B/RelA-p50 and NF kappa B/p50-p50 in control and alcohol-drinking rats subjected to carrageenin-induced pleurisy.
BACKGROUND
Carrageenin (CAR) injection into the pleural cavity causes local inflammation called carrageenin-induced pleurisy (CAR-IP). Inflammation onset is characterized by an activation of pro-inflammatory NFkappaB, RelA-p50, while inflammation resolution is characterized by an activation of an anti-inflammatory NFkappaB, p50-p50, that re-establishes homeostasis, an essential process for an organism's survival. Although chronic alcohol intake disrupts inflammation, the mechanism behind the development of inflammatory disorder in alcoholics is not yet known. Therefore, the aim of this investigation was to study the effects of ethanol intake on CAR-IP and NFkappaB activation in pleural fluid neutrophils in P rats.


METHODS
Alcohol-preferring, P rats were given free choice of alcohol (15% ethanol) and water or water alone (for control) for 15 days. Then, each rat was injected with 0.2 ml of 2% CAR into the pleural cavity under light ether anesthesia. At different time intervals after the CAR injection, rats were anesthetized and their blood and pleural fluid samples were collected. Pleural fluid inflammatory cells were identified with Turk's or Wright-Giemsa staining. Different cell types were sorted using a fluorescence-activated cell sorter. Pleural fluid neutrophils were examined for apoptosis and activation of the two NFkappaB subspecies.


RESULTS
In control rats, fluid began to accumulate in the pleural cavity 0.5 h after, which peaked 24 h after, CAR injection. Then, the values declined gradually. The increase in pleural fluid correlated with RelA-p50 activation, while the decline in pleural fluid correlated with p50-p50 activation and apoptosis in neutrophils. In alcohol-drinking rats, pleural fluid remained elevated for up to 6 days after CAR injection. Neutrophils from alcohol-drinking rats exhibited suppressed apoptosis, augmented RelA-p50 activation, and suppressed p50-p50 activation.


CONCLUSIONS
Alcohol intake prolonged inflammation in P rats. An alcohol-induced upregulation of RelA-p50 activation and downregulation of p50-p50 activation may be causally related to the alcohol-induced inflammation dysregulation.
Singh
Ashok K
AK
Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, St Paul Campus, St Paul, MN 55108, USA. singh001@umn.edu
Jiang
Yin
Y
D000428:Alcohol Drinking; D000818:Animals; D017209:Apoptosis; D002351:Carrageenan; D004586:Electrophoresis; D016328:NF-kappa B / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit; D010994:Pleura / Q000473:pathology; D010996:Pleural Effusion; D010998:Pleurisy / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D011498:Protein Precursors / Q000378:metabolism*; D051381:Rats; D013997:Time Factors; D051996:Transcription Factor RelA
D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D011498:Protein Precursors; D051996:Transcription Factor RelA; D002351:Carrageenan