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Slide 127 of 390
|Slide 127 |
|Signals in pancreatic parenchymal cells regulating the inflammatory response |
|Insults to the pancreatic acinar cell lead to upregulation of intracellular signaling systems such as nuclear factor-kB (NF-kB), activating protein-1 (AP-1) and p38 MAP kinase. The signaling systems upregulate the production of cytokines, chemokines and growth factors from the pancreatic acinar cell. The cytokines, chemokines and growth factors mediate the inflammatory response of pancreatic and activation and proliferation of stromal cells such as the stellate cell that produces extracellular matrix proteins and fibrosis. The activation of the intracellular signals can occur with supraphysiologic doses of certain cholecystokinin hormone forms (CCK) and with tumor necrosis factor a (TNFa). Ethanol treatment sensitizes the acinar cell to these stimuli so that physiologic doses of CCK or low doses of TNFa can activate the signals. These factors both activate the stellate cell and stimulate it to produce extracellular matrix, the constituent of fibrosis in chronic pancreatitis. The image also indicates that alcohol metabolism and reactive oxygen species promote activation and production of extracellular matrix by stellate cells. |
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