Colonocyte apoptosis

Intestinal inflammation In an animal model of Crohn s disease (hapten-induced cohtis), ZK-192 administered after disease onset displayed anti-inflammatory bioactions reducing TNF-, interferon-y and interleukin-8 LX modulates neutrophil transmigration across the intestinal epithelial monolayer, inhibits leukocyte rolling and adherence, modulates interleukin-8 release chemokine secretion LX inhibits TNl -o-induced nculrophil-cnlcrocyle interaction, chemokine release and colonocyte apoptosis Fiorucci et al. 2004... 

Goh J, Baird AW, O Keane C, Watson RW, Cottell D, Bernasconi G, Petasis NA, Godson C, Brady HR, MacMathuna P (2001) Lipoxin A(4) and aspirin-triggered 15-epi-lipoxin A(4) antagonize TNF-alpha-stimulated neutrophil-enterocyte interactions in vitro and attenuate TNF-alpha-induced chemokine release and colonocyte apoptosis in human intestinal mucosa ex vivo. J Immunol 167 2772-2780... 

The CaR regulates numerous biological processes, including the expression of various genes (e.g., PTH) the secretion of hormones (PTH and calcitonin), cytokines (MCP-1), and calcium (e.g., into breast milk) the activities of channels (potassium channels) and transporters (aquaporin-2) cellular shape, motility (of macrophages), and migration cellular adhesion (of hematopoietic stem cells) and cellular proliferation (of colonocytes), differentiation (of keratinocytes), and apoptosis (of H-500 ley dig cancer cells) [3]. 

Bile acids that escape enterohepatic circulation and pass to the colon can be cytotoxic to colonocytes. Damaged cells undergo apoptosis and are shed into the lumen. To maintain cell homeostasis, new cells must be produced. This replacement can result in an increase in cell proliferation rate that can increase the risk of mutations in tumor-related genes and lead to carcinoma development. Moschetta et al. (2000) showed that sphingomyelin protected against bile acid-induced cytotoxicity in human CaCo-2 colon cancer cells, a common model for studying intestinal cell function. 

Suppression of colonocyte NF-kB activation (Yin et al., 2001). NF-kB is a transcription factor that regulates several signalling patterns involved in cell proliferation and apoptosis. In many tumors activation of NF-kB promotes proliferation and inhibits apoptosis. Activation of NF-kB is also associated with inflammatory response. 

The probability p2 and p3 is proportional to the number of viable progeny of a RER+ stem cell, which depends on two parameters the number X of viable self-maintenance divisions of the stem cell (which in turn essentially depends on the threshold of mutations induced apoptosis), and the number N of mitoses that ephemeral colonocytes undergo in the crypt on their way to maturation (Fig. 4B). Since neither X (defined by the tolerable mutation load) nor N should vary at a given point in the colon, p2 and p3 should also remain constant throughout life, and likewise the product pt (p2 and p3). The accumulation of these rate-limiting steps of RER+ carcinogenesis can thus be assimilated to an accident that can happen any time with a constant risk. 

LacCer enhance EGFR activation, which in turn, leads to the phosphorylation of Akt and ERK and the up-regulation of the pro-survival protein Bcl-xL. Overall, this molecular machinery results in tire reduction of apoptosis in colonocytes, so that these surviving damaged cells develop ACF that may eventually progress into tumors. 

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