Cross-talk between oxidative stress and pro-inflammatory cytokines in acute pancreatitis: a key role for protein phosphatases.
Acute pancreatitis is an acute inflammatory process localized in the pancreatic gland that frequently involves peripancreatic tissues. It is still under investigation why an episode of acute pancreatitis remains mild affecting only the pancreas or progresses to a severe form leading to multiple organ failure and death. Proinflammatory cytokines and oxidative stress play a pivotal role in the early pathophysiological events of the disease. Cytokines such as interleukin 1beta and tumor necrosis factor alpha initiate and propagate almost all consequences of the systemic inflammatory response syndrome. On the other hand, depletion of pancreatic glutathione is an early hallmark of acute pancreatitis and reactive oxygen species are also associated with the inflammatory process. Changes in thiol homestasis and redox signaling decisively contribute to amplification of the inflammatory cascade through mitogen activated protein kinase (MAP kinase) pathways. This review focuses on the relationship between oxidative stress, pro-inflammatory cytokines and MAP kinase/protein phosphatase pathways as major modulators of the inflammatory response in acute pancreatitis. Redox sensitive signal transduction mediated by inactivation of protein phosphatases, particularly protein tyrosin phosphatases, is highlighted.
Escobar
Javier
J
Department of Physiology, University of Valencia, 46100 Burjasot (Valencia), Spain.
Pereda
Javier
J
Arduini
Alessandro
A
Sandoval
Juan
J
Sabater
Luis
L
Aparisi
Luis
L
López-Rodas
Gerardo
G
Sastre
Juan
J
D000208:Acute Disease; D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000503:physiopathology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010195:Pancreatitis / Q000503:physiopathology*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D015398:Signal Transduction
D016207:Cytokines; D020928:Mitogen-Activated Protein Kinases; D010749:Phosphoprotein Phosphatases