Cell proliferation is an important process in life for growth of normal and cancer cells. The signal transduction pathways activated during this process are strictly regulated. This editorial focuses on the role of ni...Cell proliferation is an important process in life for growth of normal and cancer cells. The signal transduction pathways activated during this process are strictly regulated. This editorial focuses on the role of nicotine, a mitogen, in the induction of signaling pathways resulting in proliferation of pancreatic tumor cells and compares these events with those in normal acinar cells isolated from the rat pancreas. The data shows striking similarities between these two cellular systems. In addition, the editorial reviews very recent literature of the contribution of MAPK signaling in cell lines associated with human diseases. A prospective cellular model of nicotine induced activation of MAPK cascade is presented.展开更多
BACKGROUND Acute pancreatitis(AP)is a sudden inflammatory process of the pancreas that may also involve surrounding tissues and/or remote organs.Inflammation and parenchymal cell death are common pathological features...BACKGROUND Acute pancreatitis(AP)is a sudden inflammatory process of the pancreas that may also involve surrounding tissues and/or remote organs.Inflammation and parenchymal cell death are common pathological features of this condition and determinants of disease severity.Polyethylene glycols(PEGs)are nonimmunogenic,non-toxic water-soluble polymers widely used in biological,chemical,clinical and pharmaceutical settings.AIM To evaluate the protective effect of a 35-kDa molecular weight PEG(PEG35)on the pancreatic damage associated to cerulein-induced acute pancreatitis in vivo and in vitro.METHODS Wistar rats were assigned at random to a control group,a cerulein–induced AP group and a PEG35 treatment group.AP was induced by five hourly intraperitoneal injections of cerulein(50μg/kg/bw),while the control animals received saline solution.PEG35 was administered intraperitoneally 10 minutes before each cerulein injection in a dose of 10 mg/kg.After AP induction,samples of pancreatic tissue and blood were collected for analysis.AR42J pancreatic acinar cells were treated with increasing concentrations of PEG35 prior to exposure with tumor necrosis factorα(TNFα),staurosporine or cerulein.The severity of AP was determined on the basis of plasma levels of lipase,lactate dehydrogenase activity,pancreatic edema and histological changes.To evaluate the extent of the inflammatory response,the gene expression of inflammation-associated markers was determined in the pancreas and in AR42J-treated cells.Inflammation-induced cell death was also measured in models of in vivo and in vitro pancreatic damage.RESULTS Administration of PEG35 significantly improved pancreatic damage through reduction on lipase levels and tissue edema in cerulein-induced AP rats.The increased associated inflammatory response caused by cerulein administration was attenuated by a decrease in the gene expression of inflammation-related cytokines and inducible nitric oxide synthase enzyme in the pancreas.In contrast,pancreatic tissue mRNA expression of interleukin 10 was markedly increased.PEG35 treatment also protected against inflammation-induced cell death by attenuating lactate dehydrogenase activity and modulating the pancreatic levels of apoptosis regulator protein BCL-2 in cerulein hyperstimulated rats.Furthermore,the activation of pro-inflammatory markers and inflammationinduced cell death in pancreatic acinar cells treated with TNFα,cerulein or staurosporine was significantly reduced by PEG35 treatment,in a dose-dependent manner.CONCLUSION PEG35 ameliorates pancreatic damage in cerulein-induced AP and AR42J-treated cells through the attenuation of the inflammatory response and associated cell death.PEG35 may be a valuable option in the management of AP.展开更多
目的:探讨Toll样受体9(Toll-like receptor 9,TLR9)在急性胰腺炎发病机制中的作用.方法:不同浓度脂多糖(lipopolysaccharide,L P S)(0、1、10、100 m g/L)刺激A R42J细胞后,RT-PCR法与Western blot法分别检测TLR9、核因子-κB(nuclear f...目的:探讨Toll样受体9(Toll-like receptor 9,TLR9)在急性胰腺炎发病机制中的作用.方法:不同浓度脂多糖(lipopolysaccharide,L P S)(0、1、10、100 m g/L)刺激A R42J细胞后,RT-PCR法与Western blot法分别检测TLR9、核因子-κB(nuclear factor-κB,NF-κB)P65 mRNA和蛋白质表达的变化,并分析TLR9、P65的相关性;ELISA法检测培养上清液白介素-1β(interleukin-1β,IL-1β)、白介素-6(interleukin-6,IL-6)含量.结果:与空白对照组相比,LPS刺激后TLR9、P65 mR N A与蛋白质表达升高,呈浓度依赖性,各组间有显著性差异(mRNA:F=21.594,F=24.449;蛋白质:F=23.193,F=24.891,均P<0.01),相关性分析:r=0.942,r=0.900,均P=0.000,TLR9、P65呈正相关.上清液IL-1β、IL-6含量随LPS浓度增加而上升,组间差异有统计学意义(F=45.459,F=62.493,均P<0.01).结论:LPS刺激AR42J细胞诱导的炎症效应中,TLR9表达上调,可能通过激活NF-κB,从而促进炎症因子合成与分泌,参与急性胰腺炎发病机制.展开更多
Cigarette smoking is a known risk factor for the development of numerous diseases. The role of nicotine in the induction of pancreatic inflammation and pancreatic cancer as a result of cigarette smoking has been recog...Cigarette smoking is a known risk factor for the development of numerous diseases. The role of nicotine in the induction of pancreatic inflammation and pancreatic cancer as a result of cigarette smoking has been recognized and reported in the literature. The mechanism by which nicotine induces such pathologies is as yet unknown. An understanding of the proliferative potential of nicotine in primary and tumor cells of the pancreas will allow us to develop measures that will ultimately lead to intervention,prevention and treatment of these diseases. Studies show that nicotine can increase the cell numbers of certain cancer cell lines,suggesting that exposure to nicotine can lead to the disruption of the dynamic balance between cell death and proliferation,which is required for normal functioning of cells. We hypothesize that nicotine induces oxidative stress in pancreatic acinar cells and thus contributes to this disruption. We have used the AR42J cell line in our study because of its stability as an immortal tumor cell line and its known physiological similarity to primary acinar cells. Our studies show that mitogen activated protein kinase signaling is induced bynicotine in AR42J cells,causing an increase in lipid peroxidation and a subsequent decrease in cell function. Our data suggest that exposure to nicotine induces oxidative stress,leading to cell injury and compromised function,thus implicating cigarette smoking as a plausible mechanism.展开更多
文摘Cell proliferation is an important process in life for growth of normal and cancer cells. The signal transduction pathways activated during this process are strictly regulated. This editorial focuses on the role of nicotine, a mitogen, in the induction of signaling pathways resulting in proliferation of pancreatic tumor cells and compares these events with those in normal acinar cells isolated from the rat pancreas. The data shows striking similarities between these two cellular systems. In addition, the editorial reviews very recent literature of the contribution of MAPK signaling in cell lines associated with human diseases. A prospective cellular model of nicotine induced activation of MAPK cascade is presented.
基金the grant from Ministerio de Ciencia e Innovación,No.PID2019-104130RB-I00.
文摘BACKGROUND Acute pancreatitis(AP)is a sudden inflammatory process of the pancreas that may also involve surrounding tissues and/or remote organs.Inflammation and parenchymal cell death are common pathological features of this condition and determinants of disease severity.Polyethylene glycols(PEGs)are nonimmunogenic,non-toxic water-soluble polymers widely used in biological,chemical,clinical and pharmaceutical settings.AIM To evaluate the protective effect of a 35-kDa molecular weight PEG(PEG35)on the pancreatic damage associated to cerulein-induced acute pancreatitis in vivo and in vitro.METHODS Wistar rats were assigned at random to a control group,a cerulein–induced AP group and a PEG35 treatment group.AP was induced by five hourly intraperitoneal injections of cerulein(50μg/kg/bw),while the control animals received saline solution.PEG35 was administered intraperitoneally 10 minutes before each cerulein injection in a dose of 10 mg/kg.After AP induction,samples of pancreatic tissue and blood were collected for analysis.AR42J pancreatic acinar cells were treated with increasing concentrations of PEG35 prior to exposure with tumor necrosis factorα(TNFα),staurosporine or cerulein.The severity of AP was determined on the basis of plasma levels of lipase,lactate dehydrogenase activity,pancreatic edema and histological changes.To evaluate the extent of the inflammatory response,the gene expression of inflammation-associated markers was determined in the pancreas and in AR42J-treated cells.Inflammation-induced cell death was also measured in models of in vivo and in vitro pancreatic damage.RESULTS Administration of PEG35 significantly improved pancreatic damage through reduction on lipase levels and tissue edema in cerulein-induced AP rats.The increased associated inflammatory response caused by cerulein administration was attenuated by a decrease in the gene expression of inflammation-related cytokines and inducible nitric oxide synthase enzyme in the pancreas.In contrast,pancreatic tissue mRNA expression of interleukin 10 was markedly increased.PEG35 treatment also protected against inflammation-induced cell death by attenuating lactate dehydrogenase activity and modulating the pancreatic levels of apoptosis regulator protein BCL-2 in cerulein hyperstimulated rats.Furthermore,the activation of pro-inflammatory markers and inflammationinduced cell death in pancreatic acinar cells treated with TNFα,cerulein or staurosporine was significantly reduced by PEG35 treatment,in a dose-dependent manner.CONCLUSION PEG35 ameliorates pancreatic damage in cerulein-induced AP and AR42J-treated cells through the attenuation of the inflammatory response and associated cell death.PEG35 may be a valuable option in the management of AP.
文摘目的:探讨Toll样受体9(Toll-like receptor 9,TLR9)在急性胰腺炎发病机制中的作用.方法:不同浓度脂多糖(lipopolysaccharide,L P S)(0、1、10、100 m g/L)刺激A R42J细胞后,RT-PCR法与Western blot法分别检测TLR9、核因子-κB(nuclear factor-κB,NF-κB)P65 mRNA和蛋白质表达的变化,并分析TLR9、P65的相关性;ELISA法检测培养上清液白介素-1β(interleukin-1β,IL-1β)、白介素-6(interleukin-6,IL-6)含量.结果:与空白对照组相比,LPS刺激后TLR9、P65 mR N A与蛋白质表达升高,呈浓度依赖性,各组间有显著性差异(mRNA:F=21.594,F=24.449;蛋白质:F=23.193,F=24.891,均P<0.01),相关性分析:r=0.942,r=0.900,均P=0.000,TLR9、P65呈正相关.上清液IL-1β、IL-6含量随LPS浓度增加而上升,组间差异有统计学意义(F=45.459,F=62.493,均P<0.01).结论:LPS刺激AR42J细胞诱导的炎症效应中,TLR9表达上调,可能通过激活NF-κB,从而促进炎症因子合成与分泌,参与急性胰腺炎发病机制.
基金Supported by the Earlier Grants from NIH and a Grant through University of Arkansas for Medical Sciences
文摘Cigarette smoking is a known risk factor for the development of numerous diseases. The role of nicotine in the induction of pancreatic inflammation and pancreatic cancer as a result of cigarette smoking has been recognized and reported in the literature. The mechanism by which nicotine induces such pathologies is as yet unknown. An understanding of the proliferative potential of nicotine in primary and tumor cells of the pancreas will allow us to develop measures that will ultimately lead to intervention,prevention and treatment of these diseases. Studies show that nicotine can increase the cell numbers of certain cancer cell lines,suggesting that exposure to nicotine can lead to the disruption of the dynamic balance between cell death and proliferation,which is required for normal functioning of cells. We hypothesize that nicotine induces oxidative stress in pancreatic acinar cells and thus contributes to this disruption. We have used the AR42J cell line in our study because of its stability as an immortal tumor cell line and its known physiological similarity to primary acinar cells. Our studies show that mitogen activated protein kinase signaling is induced bynicotine in AR42J cells,causing an increase in lipid peroxidation and a subsequent decrease in cell function. Our data suggest that exposure to nicotine induces oxidative stress,leading to cell injury and compromised function,thus implicating cigarette smoking as a plausible mechanism.
