scholarly journals ­­­Pro-inflammatory cytokines inhibit thiamin uptake by human and mouse pancreatic acinar cells: Involvement of transcriptional mechanism(s)

2020 ◽  
Author(s):  
Kasin Yadunandam Anandam ◽  
Padmanabhan Srinivasan ◽  
Tomoya Yasujima ◽  
Saleh Al-Juburi ◽  
Hamid M Said
Keyword(s):  
Inflammatory Cytokines ◽  
Mammalian Cells ◽  
Vitamin B1 ◽  
Acinar Cells ◽  
Inhibitory Effect ◽  
Significant Inhibition ◽  
Pancreatic Acinar Cells ◽  
Primary Mouse ◽  
Pro Inflammatory Cytokines

Thiamin (vitamin B1) plays critical roles in normal metabolism and function of all mammalian cells. Pancreatic acinar cells (PACs) import thiamin from circulation via specific carrier-mediated uptake that involves thiamin transporters-1 & -2 (THTR-1 & -2; products of SLC19A2 and SLC19A3, respectively). Our aim in this study was to investigate the effect(s) of pro-inflammatory cytokines on thiamin uptake by PACs. We used human primary (h)PACs, PAC 266-6 cells, and mice in vivo as models in the investigations. First, we examined the level of expression of THTR-1 & -2 mRNA in pancreatic tissues of patients with chronic pancreatitis and observed severe reduction in their expression compared to normal control subjects. Exposing hPACs and PAC 266-6 to pro-inflammatory cytokines (hyper IL-6, TNF-α, and IL-1β) was found to lead to a significant inhibition in thiamin uptake. Focusing on hyper-IL-6 (which also inhibited thiamin uptake by primary mouse PACs), the inhibition in thiamin uptake was found to be associated with significant reduction in THTR-1 & -2 proteins and mRNAs expression as well as in activity of the SLC19A2 and SLC19A3 promoters; it was also associated with reduction in level of expression of the transcription factor Sp1 (which is required for activity of these promoters). Finally, blocking the intracellular Stat3 signaling pathway was found to lead to a significant reversal in the inhibitory effect of hyper IL-6 on thiamin uptake by PAC 266-6. These results show that exposure of PACs to pro-inflammatory cytokines negatively impacts thiamin uptake via (at least in part) transcriptional mechanism(s).

scholarly journals Morphometric Measurements to Quantify the Cerulein Induced Hyperstimulatory Pancreatitis of Rats under the Protective Effect of Lectins

1998 ◽  
Vol 17 (4) ◽  
pp. 219-230 ◽  
Author(s):  
Ludwig Jonas ◽  
Ulrike Mikkat ◽  
Anke Witte ◽  
Uta Beckmann ◽  
Katrin Dölker ◽  
...  
Keyword(s):  
Protective Effect ◽  
Amylase Activity ◽  
Acinar Cells ◽  
Inhibitory Effect ◽  
Pancreatic Acinar Cells ◽  
Amylase Secretion ◽  
Ulex Europaeus ◽  
Serum Amylase Activity

In preceding papers we demonstrated an inhibitory effect of wheat germ agglutinin (WGA) and Ulex europaeus agglutinin (UEA) on the cholecystokinin (CCK) binding to the CCK receptor of rat pancreatic cells and also on the CCK induced Ca2+release and α-amylase secretionin vitroas well as on pancreatic secretion of intact ratsin vivo. In the present study we show the same inhibitory effect of both lectins on the cerulein pancreatitis of rats. This acute pancreatitis was induced by supramaximal injections (5 µg/kg/h iv or 10 µg/kg/h ip) of the CCK analogue cerulein in rats every hour. To monitor the degree of pancreatitis, we measured the number and diameter of injury vacuoles in the pancreatic acinar cells as one of the most important signs of this type of pancreatitis by light microscopic morphometry with two different systems on paraffin sections. Furthermore, the serum α-amylase activity was measured biochemically. We found a correlation between the diameter of vacuoles inside the acinar cells and the serum enzyme activity up to 24 h. The simultaneous ip administration of cerulein and WGA or UEA in a dosage of 125 µg/kg/h for 8 h led to a reduction of vacuolar diameter from 13.1 ± 2.0 µm (cerulein) to 7.5 ± 1.1 µm (cerulein + WGA) or 7.2 ± 1.3 µm (cerulein + UEA). The serum amylase activity was reduced from 63.7 ± 15.8 mmol/l \times min (cerulein) to 37.7 ± 11.8 (cerulein + WGA) or 39.4; +52.9; -31.1 (cerulein + UEA-I). Both parameters allow the grading this special type of pancreatitis to demonstrate the protective effect of the lectins.

Ethanol differentially regulates NF-κB activation in pancreatic acinar cells through calcium and protein kinase C pathways

2004 ◽  
Vol 286 (2) ◽  
pp. G204-G213 ◽  
Author(s):  
Anna S. Gukovskaya ◽  
Saeed Hosseini ◽  
Akihiko Satoh ◽  
Jason H. Cheng ◽  
Kyung J. Nam ◽  
...  
Keyword(s):  
Acinar Cells ◽  
Inhibitory Effect ◽  
Pancreatic Acinar Cells ◽  
Alcoholic Pancreatitis ◽  
Pancreatic Acini ◽  
Intracellular Ca ◽  
Ethanol Feeding ◽  
Ethanol Ethanol

Mechanisms of alcoholic pancreatitis remain unknown. Previously, we showed that ethanol feeding sensitizes rats to pancreatitis caused by CCK-8, at least in part, by augmenting activation of the proinflammatory transcription factor NF-κB. To elucidate the mechanism of sensitization, here we investigate the effect of ethanol on Ca2+- and PKC-mediated pathways of CCK-induced NF-κB activation using an in vitro system of rat pancreatic acini incubated with ethanol. Ethanol augmented CCK-8-induced activation of NF-κB, similar to our in vivo findings with ethanol-fed rats. In contrast, ethanol prevented NF-κB activation caused by thapsigargin, an agent that mobilizes intracellular Ca2+ bypassing the receptor. Pharmacological analysis showed that NF-κB activation by thapsigargin but not by CCK-8 is mediated through the calcineurin pathway and that the inhibitory effect of ethanol on the thapsigargin-induced NF-κB activation could be through inhibiting this pathway. Ethanol augmented NF-κB activation induced by the phorbol ester PMA, a direct activator of PKC. Inhibitory analysis demonstrated that Ca2+-independent (novel and/or atypical) PKC isoforms are involved in NF-κB activation induced by both CCK-8 and PMA in cells treated and not treated with ethanol. The results indicate that ethanol differentially affects the Ca2+/calcineurin- and PKC-mediated pathways of NF-κB activation in pancreatic acinar cells. These effects may play a role in the ability of ethanol to sensitize pancreas to the inflammatory response and pancreatitis.

scholarly journals Chronic Nicotine Exposure In Vivo and In Vitro Inhibits Vitamin B1 (Thiamin) Uptake by Pancreatic Acinar Cells

PLoS ONE ◽  
2015 ◽  
Vol 10 (12) ◽  
pp. e0143575 ◽  
Author(s):  
Padmanabhan Srinivasan ◽  
Edwin C. Thrower ◽  
Gopalakrishnan Loganathan ◽  
A. N. Balamurugan ◽  
Veedamali S. Subramanian ◽  
...  
Keyword(s):  
Vitamin B1 ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Nicotine Exposure ◽  
Chronic Nicotine ◽  
Exposure In Vivo

scholarly journals Effect of bacterial flagellin on thiamin uptake by human and mouse pancreatic acinar cells: inhibition mediated at the level of transcription of thiamin transporters 1 and 2

2019 ◽  
Vol 316 (6) ◽  
pp. G735-G743 ◽  
Author(s):  
Padmanabhan Srinivasan ◽  
Kasin Yadunandam Anandam ◽  
Vignesh Ramesh ◽  
Erica T. Geltz ◽  
Hamid M. Said
Keyword(s):  
Prolonged Exposure ◽  
Acinar Cells ◽  
Significant Inhibition ◽  
Pancreatic Acinar Cells ◽  
Vitamin B ◽  
Mrna Levels ◽  
Molecular Parameters ◽  
Atp Production ◽  
First Time

Thiamin (vitamin B1) is essential for normal cellular metabolism and function. Pancreatic acinar cells (PACs) obtain thiamin from the circulation via a specific carrier-mediated process that involves the plasma membrane thiamin transporters 1 and 2 (THTR-1 and THTR-2; products of SLC19A2 and SLC19A3 genes, respectively). There is nothing known about the effect of bacterial products/toxins on thiamin uptake by PACs. We addressed this issue in the present investigation by examining the effect of bacterial flagellin on physiological and molecular parameters of thiamin uptake by PACs. We used human primary PACs, mice in vivo, and cultured mouse-derived pancreatic acinar 266-6 cells in our investigation. The results showed that exposure of human primary PACs to flagellin led to a significant inhibition in thiamin uptake; this inhibition was associated with a significant decrease in expression of THTR-1 and -2 at the protein and mRNA levels. These findings were confirmed in mice in vivo as well as in cultured 266-6 cells. Subsequent studies showed that flagellin exposure markedly suppressed the activity of the SLC19A2 and SLC19A3 promoters and that this effect involved the Sp1 regulatory factor. Finally, knocking down Toll-like receptor 5 by use of gene-specific siRNA was found to lead to abrogation in the inhibitory effect of flagellin on PAC thiamin uptake. These results show, for the first time, that exposure of PACs to flagellin negatively impacts the physiological and molecular parameters of thiamin uptake and that this effect is mediated at the level of transcription of the SLC19A2 and SLC19A3 genes. NEW & NOTEWORTHY The present study demonstrates, for the first time, that prolonged exposure of pancreatic acinar cells to flagellin inhibits uptake of vitamin B1, a micronutrient that is essential for energy metabolism and ATP production. This effect is mediated at the level of transcription of the SLC19A2 and SLC19A3 genes and involves the Sp1 transcription factor.

Metformin Inhibits N-Methyl-N-Nitrosourea Induced Gastric Tumorigenesis in db/db Mice

2017 ◽  
Vol 125 (06) ◽  
pp. 392-399 ◽  
Author(s):  
Shan Zhuang ◽  
Yongmei Jian ◽  
Yongning Sun
Keyword(s):  
Gastric Cancer ◽  
Type 2 Diabetes ◽  
Inflammatory Cytokines ◽  
Serum Insulin ◽  
Inhibitory Effect ◽  
Increased Risk ◽  
Pro Inflammatory Cytokines

Abstract Type 2 diabetes can elevate risk of gastric cancer and metformin, an anti-diabetic agent, has an inhibitory effect against gastric cancer cell in vitro. However, the effect of metformin on type 2 diabetes-related gastric tumorigenesis in vivo is still not clear. In the present study, we aim to detect whether metformin can inhibit increased risk of gastric cancer in diabetic db/db mice and which the potential anti-cancer mechanisms of metformin are. 4-week-old mice were divided into 3 groups (2 db/db mice groups and one wild type mice group). All diabetic and non-diabetic mice were treated with N-Methyl-N-Nitrosourea (MNU) for 20 weeks to induce gastric tumorigenesis. At week 21, one db/db mice group were treated with metformin (5 mg/ml) for 10 weeks and the other 2 groups were treated with saline. Blood samples were collected for testing insulin and insulin-like growth factor (IGF)-1. Stomach tissues were collected for histopathological evaluation and mRNAs analysis. Metformin significantly decreased incidence of MNU-induced gastric dysplasia and cancer in diabetic db/db mice. Furthermore, metformin reduced serum insulin as well as IGF-1, and also suppressed expression of insulin receptor, IGF-1, IGF-1 receptor and several pro-inflammatory cytokines mRNAs in stomach of db/db mice, but did not significantly influence IGF-2 and IGF-2 receptor expressions. The results show that metformin can prevent the risk of gastric cancer in type 2 diabetes and the protective mechanisms may involve in an inhibitory effect of metformin on insulin as well as IGF-1 signals and cancer related pro-inflammatory cytokines.

Methylmercury-induced pro-inflammatory cytokines activation and its preventive strategy using anti-inflammation N-acetyl-l-cysteine: a mini-review

2020 ◽  
Vol 35 (3) ◽  
pp. 233-238
Author(s):  
Muflihatul Muniroh
Keyword(s):  
Inflammatory Cytokines ◽  
Health Concern ◽  
Brain Cells ◽  
Preventive Strategy ◽  
Hearing Impairments ◽  
Sensory Disturbances ◽  
Anti Inflammation ◽  
Pro Inflammatory Cytokines

AbstractThe exposure of methylmercury (MeHg) has become a public health concern because of its neurotoxic effect. Various neurological symptoms were detected in Minamata disease patients, who got intoxicated by MeHg, including paresthesia, ataxia, gait disturbance, sensory disturbances, tremors, visual, and hearing impairments, indicating that MeHg could pass the blood-brain barrier (BBB) and cause impairment of neurons and other brain cells. Previous studies have reported some expected mechanisms of MeHg-induced neurotoxicity including the neuroinflammation pathway. It was characterized by the up-regulation of numerous pro-inflammatory cytokines expression. Therefore, the use of anti-inflammatories such as N-acetyl-l-cysteine (NAC) may act as a preventive compound to protect the brain from MeHg harmful effects. This mini-review will explain detailed information on MeHg-induced pro-inflammatory cytokines activation as well as possible preventive strategies using anti-inflammation NAC to protect brain cells, particularly in in vivo and in vitro studies.

scholarly journals A novel application of bubble-eye strain of Carassius auratus for ex vivo fish immunological studies

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hiroto Nakajima ◽  
Atsushi Miyashita ◽  
Hiroshi Hamamoto ◽  
Kazuhisa Sekimizu
Keyword(s):  
Inflammatory Cytokines ◽  
Immune Cells ◽  
Ex Vivo ◽  
Large Bubble ◽  
Suitable Model ◽  
Bacterial Cells ◽  
Functional Impairments ◽  
Gene Expressions ◽  
Pro Inflammatory Cytokines

AbstractIn this study, we investigated a new application of bubble-eye goldfish (commercially available strain with large bubble-shaped eye sacs) for immunological studies in fishes utilizing the technical advantage of examining immune cells in the eye sac fluid ex vivo without sacrificing animals. As known in many aquatic species, the common goldfish strain showed an increased infection sensitivity at elevated temperature, which we demonstrate may be due to an immune impairment using the bubble-eye goldfish model. Injection of heat-killed bacterial cells into the eye sac resulted in an inflammatory symptom (surface reddening) and increased gene expression of pro-inflammatory cytokines observed in vivo, and elevated rearing temperature suppressed the induction of pro-inflammatory gene expressions. We further conducted ex vivo experiments using the immune cells harvested from the eye sac and found that the induced expression of pro-inflammatory cytokines was suppressed when we increased the temperature of ex vivo culture, suggesting that the temperature response of the eye-sac immune cells is a cell autonomous function. These results indicate that the bubble-eye goldfish is a suitable model for ex vivo investigation of fish immune cells and that the temperature-induced infection susceptibility in the goldfish may be due to functional impairments of immune cells.

scholarly journals Chronic alcohol exposure inhibits biotin uptake by pancreatic acinar cells: possible involvement of epigenetic mechanisms

2014 ◽  
Vol 307 (9) ◽  
pp. G941-G949 ◽  
Author(s):  
Padmanabhan Srinivasan ◽  
Rubina Kapadia ◽  
Arundhati Biswas ◽  
Hamid M. Said
Keyword(s):  
Transgenic Mice ◽  
Chronic Exposure ◽  
Methylation Status ◽  
Acinar Cells ◽  
Alcohol Exposure ◽  
Significant Inhibition ◽  
Pancreatic Acinar Cells ◽  
Chronic Alcohol ◽  
Wild Type ◽  
Chronic Alcohol Exposure

Chronic exposure to alcohol affects different physiological aspects of pancreatic acinar cells (PAC), but its effect on the uptake process of biotin is not known. We addressed this issue using mouse-derived pancreatic acinar 266-6 cells chronically exposed to alcohol and wild-type and transgenic mice (carrying the human SLC5A6 5′-promoter) fed alcohol chronically. First we established that biotin uptake by PAC is Na+ dependent and carrier mediated and involves sodium-dependent multivitamin transporter (SMVT). Chronic exposure of 266-6 cells to alcohol led to a significant inhibition in biotin uptake, expression of SMVT protein, and mRNA as well as in the activity of the SLC5A6 promoter. Similarly, chronic alcohol feeding of wild-type and transgenic mice carrying the SLC5A6 promoter led to a significant inhibition in biotin uptake by PAC, as well as in the expression of SMVT protein and mRNA and the activity of the SLC5A6 promoters expressed in the transgenic mice. We also found that chronic alcohol feeding of mice is associated with a significant increase in the methylation status of CpG islands predicted to be in the mouse Slc5a6 promoters and a decrease in the level of expression of transcription factor KLF-4, which plays an important role in regulating SLC5A6 promoter activity. These results demonstrate, for the first time, that chronic alcohol exposure negatively impacts biotin uptake in PAC and that this effect is exerted (at least in part) at the level of transcription of the SLC5A6 gene and may involve epigenetic/molecular mechanisms.

Sa615 TRANSPLANTATION OF FUSOBACTERIUM VARIUM IN VIVO RESULTS IN AN INCREASE OF PRO-INFLAMMATORY CYTOKINES AND STOOL WET WEIGHT

2021 ◽  
Vol 160 (6) ◽  
pp. S-574-S-575
Author(s):  
Maria Jesus Villanueva-Millan ◽  
Maritza Sanchez ◽  
Walter Morales ◽  
Gabriela Leite ◽  
Stacy Weitsman ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Wet Weight ◽  
Fusobacterium Varium ◽  
Pro Inflammatory Cytokines

scholarly journals Inhibitory effect of high leucine concentration on α-amylase secretion by pancreatic acinar cells: possible key factor of proteasome

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Long Guo ◽  
Baolong Liu ◽  
Chen Zheng ◽  
Hanxun Bai ◽  
Hao Ren ◽  
...  
Keyword(s):  
Amylase Activity ◽  
Acinar Cells ◽  
Inhibitory Effect ◽  
Proteasome Activity ◽  
Pancreatic Acinar Cells ◽  
Amylase Secretion ◽  
High Concentration ◽  
Amylase Release ◽  
Cholecystokinin Receptor ◽  
Key Factor

The present study aimed to investigate whether leucine affects the pancreatic exocrine by controlling the antisecretory factor (AF) and cholecystokinin receptor (CCKR) expression as well as the proteasome activity in pancreatic acinar cells of dairy calves. The pancreatic acinar cells were isolated from newborn Holstein bull calves and cultured using the Dulbecco’s modified Eagle’s medium/nutrient mixture F12 Ham’s liquid (DMEM/F12). There were six treatments of leucine dosage including 0 (control), 0.23, 0.45, 1.35, 4.05, and 12.15 mM, respectively. After culture for 3 h, the samples were collected for subsequent analysis. As the leucine concentration increased from 0 to 1.35 mM, the α-amylase activity in media decreased significantly (P<0.05), while further increase in leucine concentration did not show any decrease in α-amylase activity. Addition of leucine inhibited (P<0.05) the expression of AF and CCKR, and decreased the activity of proteasome (P<0.05) by 76%, 63%, 24%, 7%, and 9%, respectively. Correlation analysis results showed α-amylase secretion was negatively correlated with leucine concentration (P<0.01), and positively correlated with proteasome activity (P<0.01) and the expression of CCK1R (P<0.01) and AF (P<0.05). The biggest regression coefficient was showed between α-amylase activity and proteasome (0.7699, P<0.001). After inhibition of proteasome by MG-132, low dosage leucine decreased (P<0.05) the activity of proteasome and α-amylase, as well as the expression of CCK1R. In conclusion, we demonstrated that the high-concentration leucine induced decrease in α-amylase release was mainly by decreasing proteasome activity.

Sign in / Sign up

Export Citation Format

Share Document