Chronic pancreatic inflammation induced by environmental tobacco smoke inhalation in rats.
OBJECTIVE
Despite a strong epidemiological association between cigarette smoking and pancreatic diseases, such as pancreatic cancer and chronic pancreatitis, the effects of long-term cigarette smoke inhalation on the pancreas have not been clearly determined. In the present study, we investigated the effect of cigarette smoke inhalation on the pancreas.


METHODS
Thirty-six female Sprague Dawley rats were exposed to two different doses of environmental tobacco smoke averaging 100 mg or 160 mg/m3 total suspended particulate matter (TSP) per m3 for 70 min twice a day for 12 wk. The animals were sacrificed and examined for the effects of tobacco smoke exposure on pancreatic morphology and function.


RESULTS
In 58% (7/12) of the animals, exposure to 160 mg/m3 TSP cigarette smoke induced a chronic pancreatic inflammatory process with fibrosis and scarring of pancreatic acinar structures. Animals with fibrotic alterations showed an induction of pancreatic pro-collagen 1 gene expression, and the infiltration of immune cells was accompanied by the expression of the inflammatory mediators MIP-1alpha, IL-1beta, and TGF-beta in 33% (4/12) of the animals. Acinar cell stress was manifested by a significant up-regulation of pancreatitis-associated protein expression (PAP) in smoke-exposed animals (smoke-exposed 6,932 +/- 1,236 vs control 3,608 +/- 305, p < 0.05). Possibly contributing to the morphological damage to the exocrine pancreas, the inhalation of cigarette smoke induced trypsinogen and chymotrypsinogen gene expression and, furthermore, reduced pancreatic enzyme content.


CONCLUSIONS
This study provides experimental evidence of morphological pancreatic damage induced by the inhalation of cigarette smoke, which is likely to be mediated by alterations of acinar cell function.
Wittel
Uwe A
UA
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska 68198-5870, USA.
Pandey
Krishan K
KK
Andrianifahanana
Mahefatiana
M
Johansson
Sonny L
SL
Cullen
Diane M
DM
Akhter
Mohammed P
MP
Brand
Randall E
RE
Prokopczyk
Bogdain
B
Batra
Surinder K
SK
D000818:Animals; D001707:Biopsy, Needle; D003367:Cotinine / Q000032:analysis / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D007150:Immunohistochemistry; D009538:Nicotine / Q000032:analysis / Q000378:metabolism; D010186:Pancreatic Function Tests; D050500:Pancreatitis, Chronic / Q000209:etiology* / Q000473:pathology*; D000073718:Pancreatitis-Associated Proteins; D011336:Probability; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012307:Risk Factors; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human; D014028:Tobacco Smoke Pollution; D009538:Nicotine; D003367:Cotinine