Smoking Is Related to Pancreatic Fibrosis in Humans

Geenen, Erwin J M van; Smits, Mark M.; Schreuder, T.C.M.A.; Peet, Donald L. van der; Bloemena, Elisabeth; Mulder, Chris J.J.

doi:10.1038/ajg.2011.43

Cited by 68 publications

(38 citation statements)

References 44 publications

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“…The increased activation of PSCs in response to smoke exposure was corroborated by previous work documenting higher levels of pancreatic fibrosis in smokers compared with never smokers. 46 The increased levels of IL-12p40 cytokine secreted by DCs matured explicitly in response to ATRA, suggesting the involvement of ATRA in smoking-mediated immune modulation. 47 …”

Section: Discussionmentioning

confidence: 98%

Smoking accelerates pancreatic cancer progression by promoting differentiation of MDSCs and inducing HB-EGF expression in macrophages

et al. 2014

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Smoking is an established risk factor for pancreatic cancer (PC), but late diagnosis limits the evaluation of its mechanistic role in the progression of PC. We used a well-established genetically engineered mouse model (LSL-K-rasG12D) of PC to elucidate the role of smoking during initiation and development of pancreatic intraepithelial neoplasia (PanIN). The 10-week-old floxed mice (K-rasG12D; Pdx-1cre) and their control unfloxed (LSL-K-rasG12D) littermates were exposed to cigarette smoke (total suspended particles: 150 mg/m3) for 20 weeks. Smoke exposure significantly accelerated the development of PanIN lesions in the floxed mice, which correlated with tenfold increase in the expression of cytokeratin19. The systemic accumulation of myeloid-derived suppressor cells (MDSCs) decreased significantly in floxed mice compared with unfloxed controls (P<0.01) after the smoke exposure with the concurrent increase in the macrophage (P<0.05) and dendritic cell (DCs) (P<0.01) population. Further, smoking-induced inflammation (IFN-γ, CXCL2; P<0.05) was accompanied by enhanced activation of pancreatic stellate cells and elevated levels of serum retinoic acid-binding protein 4, indicating increased bioavailability of retinoic acid which contributes to differentiation of MDSCs to tumor-associated macrophages (TAMs) and DCs. TAMs predominantly contribute to the increased expression of heparin-binding epidermal growth factor-like growth factor (EGFR ligand) in pre-neoplastic lesions in smoke-exposed floxed mice that facilitate acinar-to-ductal metaplasia (ADM). Further, smoke exposure also resulted in partial suppression of the immune system early during PC progression. Overall, the present study provides a novel mechanism of smoking-induced increase in ADM in the presence of constitutively active K-ras mutation.

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Section: Discussionmentioning

confidence: 98%

Smoking accelerates pancreatic cancer progression by promoting differentiation of MDSCs and inducing HB-EGF expression in macrophages

et al. 2014

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“…It is furthermore suggested that smoking increases progression of fibrosis in other organ systems, including the pancreas, kidneys, lungs and heart [23][24][25][26].…”

Section: Discussionmentioning

confidence: 99%

Smoking is associated with severity of liver fibrosis but not with histological severity in nonalcoholic fatty liver disease. Results from a cross-sectional study

Munsterman

Smits

Andriessen

et al. 2017

Scandinavian Journal of Gastroenterology

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“…Concerning pancreatic disease, cigarette smoking may induce fibrosis and metastasis, hallmarks of chronic pancreatitis and pancreatic adenocarcinoma, respectively [22] . Evidence suggests that protein expression is altered in pancreatic duct cells (PaDC), and such cellular changes are implicated in pancreatic cancer and chronic pancreatitis [23].…”

Section: Introductionmentioning

confidence: 99%

Nicotine Alters the Proteome of Two Human Pancreatic Duct Cell Lines

Paulo

2014

JOP. Journal of the Pancreas

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Smoking Is Related to Pancreatic Fibrosis in Humans

Abstract: To our knowledge, no study in humans had studied the effect of tobacco smoking on pancreatic tissue. We have demonstrated for the first time that current cigarette smoking is associated with total PF-specifically, intralobular PF-as compared with nonsmokers.

Cited by 68 publications

References 44 publications

Smoking accelerates pancreatic cancer progression by promoting differentiation of MDSCs and inducing HB-EGF expression in macrophages

Smoking accelerates pancreatic cancer progression by promoting differentiation of MDSCs and inducing HB-EGF expression in macrophages

Smoking is associated with severity of liver fibrosis but not with histological severity in nonalcoholic fatty liver disease. Results from a cross-sectional study

Nicotine Alters the Proteome of Two Human Pancreatic Duct Cell Lines

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