Alcohol and Cigarette Smoke Components Activate Human Pancreatic Stellate Cells: Implications for the Progression of Chronic Pancreatitis

作者：Lee Alexandra T K; Xu Zhihong; Pothula Srinivasa P; Patel Mishaal B; Pirola Romano C; Wilson Jeremy S; Apte Minoti V^*

来源：Alcoholism: Clinical and Experimental Research , 2015, 39(11): 2123-2133.

DOI：10.1111/acer.12882

• Alcohol
• Smoking
• Pancreatic Stellate Cells
• Pancreatic Fibrosis
• Chronic Pancreatitis

BackgroundChronic pancreatitis, a known complication of alcohol abuse, is characterized histopathologically by prominent fibrosis. Pancreatic stellate cells (PSCs) are responsible for producing this fibrous tissue in chronic pancreatitis and are activated by alcohol. Progression of alcoholic chronic pancreatitis (as assessed by calcification and fibrosis) is thought to be facilitated by concurrent smoking, but the mechanisms are unknown. This study aimed to (a) determine whether human PSCs (hPSCs) and rat PSCs express nicotinic acetylcholine receptors (nAChRs), which are known to bind 2 important components of cigarette smoke, namely nicotine and nicotine-derived nitrosamine ketone (NNK), and (b) examine the effects of cigarette smoke components in the presence and absence of alcohol on PSC activation invitro.
MethodsWestern blotting was used to detect the presence of nAChRs in primary cultures of PSCs. Clinically relevant concentrations of cigarette smoke components (either cigarette smoke extract [CSE], NNK, or nicotine)ethanol (EtOH) were used to treat primary cultures of PSCs, and stellate cell activation was assessed by cell migration, proliferation, collagen production, and apoptosis.
ResultsWe demonstrate, for the first time, that PSCs express nAChRs (isoforms 3, 7, , epsilon) and that the expression of the 7 isoform in hPSCs is induced by CSE+EtOH. We also providenovel findings that PSCs are activated by CSE and NNK (both alone and in combination with EtOH) as evidenced by an increase in cell migration and/or proliferation. Further, we demonstrate that activation of PSCs by CSE+EtOH and NNK + EtOH may be mediated via nAChRs on the cells.
ConclusionsPSCs are activated by clinically relevant concentrations of cigarette smoke components (CSE and NNK), alone and in combination with EtOH. Thus, in alcoholics who smoke, progression of pancreatic fibrosis may be facilitated by the combined effects of alcohol and cigarette smoke components on hPSC behavior.

• 出版日期2015-11