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Alcohol and Cigarette Smoke Components Activate Human Pancreatic Stellate Cells: Implications for the Progression of Chronic Pancreatitis
Author(s) -
Lee Alexandra T. K.,
Xu Zhihong,
Pothula Srinivasa P.,
Patel Mishaal B.,
Pirola Romano C.,
Wilson Jeremy S.,
Apte Minoti V.
Publication year - 2015
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.12882
Subject(s) - hepatic stellate cell , pancreatitis , nicotine , chemistry , cancer research , fibrosis , pancreatitis, chronic , endocrinology , medicine , pharmacology
Background Chronic pancreatitis, a known complication of alcohol abuse, is characterized histopathologically by prominent fibrosis. Pancreatic stellate cells ( PSC s) 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 PSC s express nicotinic acetylcholine receptors ( nAChR s), 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 in vitro. Methods Western blotting was used to detect the presence of nAChR s in primary cultures of PSC s. Clinically relevant concentrations of cigarette smoke components (either cigarette smoke extract [ CSE ], NNK , or nicotine) ± ethanol (EtOH) were used to treat primary cultures of PSC s, and stellate cell activation was assessed by cell migration, proliferation, collagen production, and apoptosis. Results We demonstrate, for the first time, that PSC s express nAChR s (isoforms α 3, α 7, β , ε ) and that the expression of the α 7 isoform in hPSC s is induced by CSE + EtOH. We also provide novel findings that PSC s 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 PSC s by CSE + EtOH and NNK + EtOH may be mediated via nAChR s on the cells. Conclusions PSCs 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.