Ibuprofen and diclofenac treatments reduce proliferation of pancreatic acinar cells upon inflammatory injury and mitogenic stimulation
| Autor: | Rolf Graf, Alina Rudnicka, Sabrina Sonda, Rong Chen, Marta Bombardo, Ermanno Malagola |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Pharmacology Acinar cell proliferation medicine.medical_specialty business.industry Macrophage polarization medicine.disease digestive system 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Endocrinology Diclofenac 030220 oncology & carcinogenesis Internal medicine Cancer cell medicine Acinar cell Acute pancreatitis Pancreatitis business Ceruletide medicine.drug |
| Zdroj: | British Journal of Pharmacology. 175:335-347 |
| ISSN: | 0007-1188 |
| Popis: | Background and Purpose Nonsteroidal anti-inflammatory drugs (NSAIDs) are administered to manage pain typically found in patients suffering from pancreatitis. NSAIDs also display anti-proliferative activity against cancer cells, however their effects in normal, untransformed cells is poorly understood. Here we evaluated whether NSAIDs inhibit proliferation of pancreatic acinar cells during the development of acute pancreatitis. Experimental Approach The NSAIDs ibuprofen and diclofenac were administered to C57BL/6 mice after induction of pancreatitis with serial injection of cerulein. In addition, ibuprofen was administered concomitantly to 3,5,3-L-tri-iodothyronine (T3), which induces acinar cell proliferation in the absence of tissue inflammation. Development of pancreatic inflammation, acinar de-differentiation into metaplastic lesions and acinar proliferation were quantified by histochemical, biochemical and RT-PCR approaches. Key Results Therapeutic ibuprofen treatment selectively reduced pancreatic infiltration of activated macrophages in vivo, M1 macrophage polarization and pro-inflammatory cytokine expression both in vivo and in vitro. Reduced macrophage activation was accompanied by reduced acinar de-differentiation into acinar-to-ductal metaplasia. Acinar proliferation was significantly impaired in the presence of ibuprofen and diclofenac, evidenced both at the level of proliferation markers and expression of cell cycle regulators. Ibuprofen treatment also reduced acinar cell proliferation induced upon mitogenic stimulation with T3, a treatment that does not elicit pancreatic inflammation. Conclusions and Implications Our study provides evidence that the NSAIDs ibuprofen and diclofenac inhibit pancreatic acinar cell division. This suggests that prolonged treatment with these NSAIDs may negatively affect the extent of pancreatic regeneration and further studies are needed to confirm these findings in a clinical setting. |
| Databáze: | OpenAIRE |
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