FIGURE 1.

Cystic fibrosis transmembrane conductance regulator (CFTR) expression and activity are decreased in smokers and in chronic pancreatitis (CP) patients. (A) Cl_sw ^– was significantly higher in smoking patients (n = 16) compared to non‐smoking controls (n = 20). There is a significant difference in CP (n = 12) versus the control patients. Further elevation in sweat Cl^– concentration (Cl_sw ^–) was observed in the smoking CP (n = 19) patients compared to the CP group. (B) Expression analysis showed that incubation of human pancreatic organoid cultures with 80 µg/mL cigarette smoke extract (CSE) significantly reduced the mRNA expression of CFTR. Expression levels were calculated relative to the POLII gene. (C) Representative confocal images showed that smoking significantly reduced CFTR expression on the apical membrane of pancreatic ductal epithelial cells in tissues from the human non‐smoker and smoker cadaver donors (n = 3). Scale bar = 50 µm. (D) The intensity profile confirmed that apical CFTR distribution was impaired in response to smoking. CFTR staining density at the luminal membrane was decreased in the smoking CP patients (H), whereas there was no significant difference in cytoplasmic density of CFTR between the non‐smoker CP (G) and smoker CP groups (n = 3). EC: cytoplasm; M: membrane. Scale bar = 50 µm. Exact p‐values are indicated above each column. (E) Analysis of the human serum samples showed that their mercury (Hg) content was significantly higher in smoker groups, both in the control and CP patients (n = 7−10). No significant difference in serum cadmium (Cd) concentration was observed between the non‐smoker (n = 9) and smoker (n = 7) controls. However, there was a significantly higher Cd concentration in the smoking CP (n = 10) versus non‐smoking CP (n = 10) patients. (F) Cd level was significantly higher in human pancreatic tissue samples derived from the smoker compared to the non‐smoker cadaver donors (n = 3).