scholarly journals Non-steroidol anti-inflammatory drug effect on crypt cell proliferation and apoptosis during initiation of rat colon carcinogenesis

1998 ◽  
Vol 77 (4) ◽  
pp. 573-580 ◽  
Author(s):  
CJ Barnes ◽  
IL Cameron ◽  
WE Hardman ◽  
M Lee
Keyword(s):  
Cell Proliferation ◽  
Drug Effect ◽  
Colon Carcinogenesis ◽  
Crypt Cell ◽  
Rat Colon ◽  
Inflammatory Drug ◽  
Crypt Cell Proliferation ◽  
Proliferation And Apoptosis ◽  
Anti Inflammatory

Interleukin-10-independent anti-inflammatory actions of glucagon-like peptide 2

2008 ◽  
Vol 295 (6) ◽  
pp. G1202-G1210 ◽  
Author(s):  
Catherine P. A. Ivory ◽  
Laurie E. Wallace ◽  
Donna-Marie McCafferty ◽  
David L. Sigalet
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Lamina Propria ◽  
Interleukin 10 ◽  
Crypt Cell ◽  
Intestinal Epithelial ◽  
Crypt Cell Proliferation ◽  
Tnf Α ◽  
Glucagon Like Peptide ◽  
Anti Inflammatory

Glucagon-like peptide 2 (GLP-2) is an important intestinal growth factor with anti-inflammatory activity. We hypothesized that GLP-2 decreases mucosal inflammation and the associated increased epithelial proliferation by downregulation of Th1 cytokines attributable to reprogramming of lamina propria immune regulatory cells via an interleukin-10 (IL-10)-independent pathway. The effects of GLP-2 treatment were studied using the IL-10-deficient (IL-10−/−) mouse model of colitis. Wild-type and IL-10−/− mice received saline or GLP-2 (50 μg/kg sc) treatment for 5 days. GLP-2 treatment resulted in significant amelioration of animal weight loss and reduced intestinal inflammation as assessed by histopathology and myeloperoxidase levels compared with saline-treated animals. In colitis animals, GLP-2 treatment also reduced crypt cell proliferation and crypt cell apoptosis. Proinflammatory (IL-1β, TNF-α, IFN-γ,) cytokine protein levels were significantly reduced after GLP-2 treatment, whereas IL-4 was significantly increased and IL-6 production was unchanged. Fluorescence-activated cell sorting analysis of lamina propria cells demonstrated a decrease in the CD4+ T cell population following GLP-2 treatment in colitic mice and an increase in CD11b+/F4/80+ macrophages but no change in CD25+FoxP3 T cells or CD11c+ dendritic cells. In colitis animals, intracellular cytokine analysis demonstrated that GLP-2 decreased lamina propria macrophage TNF-α production but increased IGF-1 production, whereas transforming growth factor-β was unchanged. GLP-2-mediated reduction of crypt cell proliferation was associated with an increase in intestinal epithelial cell suppressor of cytokine signaling (SOCS)-3 expression and reduced STAT-3 signaling. This study shows that the anti-inflammatory effects of GLP-2 are IL-10 independent and that GLP-2 alters the mucosal response of inflamed intestinal epithelial cells and macrophages. In addition, the suggested mechanism of the reduction in inflammation-induced proliferation is attributable to GLP-2 activation of the SOCS-3 pathway, which antagonizes the IL-6-mediated increase in STAT-3 signaling.

Reduction of mucosal crypt cell proliferation in patients with colorectal adenomatous polyps by dietary calcium supplementation

1992 ◽  
Vol 79 (6) ◽  
pp. 581-583 ◽  
Author(s):  
G. H. Barsoum ◽  
C. Hendrickse ◽  
M. C. Winslet ◽  
D. Youngs ◽  
I. A. Donovan ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Calcium Supplementation ◽  
Dietary Calcium ◽  
Crypt Cell ◽  
Adenomatous Polyps ◽  
Crypt Cell Proliferation

scholarly journals Glucagon-Like Peptide-2 Activates β-Catenin Signaling in the Mouse Intestinal Crypt: Role of Insulin-Like Growth Factor-I

Endocrinology ◽  
2007 ◽  
Vol 149 (1) ◽  
pp. 291-301 ◽  
Author(s):  
Philip E. Dubé ◽  
Katherine J. Rowland ◽  
Patricia L. Brubaker
Keyword(s):  
Cell Proliferation ◽  
Nuclear Translocation ◽  
Glycogen Synthase ◽  
Crypt Cell ◽  
Acute Administration ◽  
Intestinal Crypt ◽  
Crypt Cell Proliferation ◽  
Igf I ◽  
Glucagon Like Peptide ◽  
Crypt Cells

Chronic administration of glucagon-like peptide-2 (GLP-2) induces intestinal growth and crypt cell proliferation through an indirect mechanism requiring IGF-I. However, the intracellular pathways through which IGF-I mediates GLP-2-induced epithelial tropic signaling remain undefined. Because β-catenin and Akt are important regulators of crypt cell proliferation, we hypothesized that GLP-2 activates these signaling pathways through an IGF-I-dependent mechanism. In this study, fasted mice were administered Gly2-GLP-2 or LR3-IGF-I (positive control) for 0.5–4 h. Nuclear translocation of β-catenin in non-Paneth crypt cells was assessed by immunohistochemistry and expression of its downstream proliferative markers, c-myc and Sox9, by quantitative RT-PCR. Akt phosphorylation and activation of its targets, glycogen synthase kinase-3β and caspase-3, were determined by Western blot. IGF-I receptor (IGF-IR) and IGF-I signaling were blocked by preadministration of NVP-AEW541 and through the use of IGF-I knockout mice, respectively. We found that GLP-2 increased β-catenin nuclear translocation in non-Paneth crypt cells by 72 ± 17% (P < 0.05) and increased mucosal c-myc and Sox9 mRNA expression by 90 ± 20 and 376 ± 170%, respectively (P < 0.05–0.01), with similar results observed with IGF-I. This effect of GLP-2 was prevented by blocking the IGF-IR as well as ablation of IGF-I signaling. GLP-2 also produced a time- and dose-dependent activation of Akt in the intestinal mucosa (P < 0.01), most notably in the epithelium. This action was reduced by IGF-IR inhibition but not IGF-I knockout. We concluded that acute administration of GLP-2 activates β-catenin and proliferative signaling in non-Paneth murine intestinal crypt cells as well as Akt signaling in the mucosa. However, IGF-I is required only for the GLP-2-induced alterations in β-catenin.

Vitamin A deficiency inhibits intestinal adaptation by modulating apoptosis, proliferation, and enterocyte migration

2003 ◽  
Vol 285 (2) ◽  
pp. G424-G432 ◽  
Author(s):  
Deborah A. Swartz-Basile ◽  
Lihua Wang ◽  
Yuzhu Tang ◽  
Henry A. Pitt ◽  
Deborah C. Rubin ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Small Bowel ◽  
Vitamin A ◽  
Vitamin A Deficiency ◽  
Intestinal Adaptation ◽  
Collagen Iv ◽  
Crypt Cell ◽  
Migration Rates ◽  
Crypt Cell Proliferation ◽  
Extracellular Matrix Components

In a prior study, vitamin A-deficient rats subjected to submassive small bowel resections did not mount a normal intestinal adaptive response by 10 days postoperatively, although adaptive increases in crypt cell proliferation were not attenuated and there were no differences in apoptotic indexes. The present study was designed to address the mechanisms by which vitamin A status effects adaptation by analyzing proliferation, apoptosis, and enterocyte migration in the early postoperative period (16 and 48 h) in vitamin A-sufficient, -deficient, and partially replenished sham-resected and resected rats. At 16 h postresection, apoptosis was significantly greater in the remnant ileum of resected vitamin A-deficient rats compared with the sufficient controls. Crypt cell proliferation was increased by resection in all dietary groups at both timepoints. However, at 48 h postresection, proliferation was significantly decreased in the vitamin A-deficient and partially replenished rats. By 48 h after resection, vitamin A deficiency also reduced enterocyte migration rates by 44%. This occurred in conjunction with decreased immunoreactive collagen IV at 48 h and 10 days postoperation. Laminin expression was also reduced by deficiency at 10 days postresection, whereas fibronectin and pancadherin were unchanged at 48 h and 10 days. These studies indicate that vitamin A deficiency inhibits intestinal adaptation following partial small bowel resection by reducing crypt cell proliferation, by enhancing early crypt cell apoptosis, and by markedly reducing enterocyte migration rates, which may be related to changes in the expression of collagen IV and other extracellular matrix components.

scholarly journals Effects of Watermelon Consumption on Cellular Proliferation, and Apoptosis in Rat Colon (P05-019-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Meseret Fesseha ◽  
Mee Young Hong
Keyword(s):  
Colon Cancer ◽  
Cell Proliferation ◽  
Cellular Proliferation ◽  
Dietary Intervention ◽  
Citrullus Lanatus ◽  
Proliferation Index ◽  
Cancer Center ◽  
Rat Colon ◽  
Proliferative Zone ◽  
Proliferation And Apoptosis

Abstract Objectives Colon Cancer is the second deadliest cancerous disease worldwide among men and women. It has been estimated that more than half of colon cancers may be preventable by dietary intervention. A disturbance of the homeostasis between cellular proliferation and apoptosis is associated with colon cancer development. Watermelon (Citrullus lanatus) is rich in L-citrulline, a precursor of L-arginine. It has been shown that L-arginine may have anti-inflammatory roles and serves as a substrate for synthesis of nitric oxide, which in turn exerts wide-ranging physiological effects including tumoricidal effects via modification of cell kinetics. Our research examined if colon cancer can be prevented with the supplementation of watermelon powder by lowering cellular proliferation but enhancing apoptosis. Methods In order to test the hypothesis, 21-days old 32 Sprague Dawley rats were allocated to three groups; control, L- arginine (0.36% L-arginine) and watermelon powder (0.5%, w/w). Carcinogen azoxymethane was injected at week 4 and 5, and colon tissues were harvested at 5 week after the 2nd carcinogen injection. Cell proliferation and apoptosis were enumerated using a quantitative immunohistochemical analysis of Ki-67 antibody and TUNEL assay, respectively. Results Cell proliferation was mainly located bottom of colonic crypt (P < 0.05). Apoptotic cells were mostly located in the upper part of crypt (P < 0.05). L-arginine and watermelon fed rats lowered cell proliferation index and proliferative zone (P < 0.05). However, no difference was found on apoptosis among the three groups. Conclusions These results suggest that watermelon powder supplementation may reduce the risk of colon cancer by reducing cell proliferation rather than alteration of apoptosis. Further study will follow to determine the mechanism of anti-proliferative effect of watermelon supplementation. Funding Sources National Watermelon Promotion Board; SDSU/UCSD Cancer Center Partnership Scholars Program.

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