NF-κB in acute pancreatitis: Mechanisms and therapeutic potential
| Autor: | B. Ratnakar Reddy, Sasikala Mitnala, Rupjyoti Talukdar, Ramaiah Jangala, D. Nageshwar Reddy, Aparna Jakkampudi |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Endocrinology Diabetes and Metabolism Inflammation Pharmacology Systemic inflammation Pathogenesis 03 medical and health sciences chemistry.chemical_compound Pyrrolidine dithiocarbamate medicine Humans Hepatology Platelet-activating factor Pancreatitis Acute Necrotizing business.industry NF-kappa B Gastroenterology medicine.disease Systemic inflammatory response syndrome 030104 developmental biology chemistry Immunology Proteasome inhibitor Cytokines Acute pancreatitis I-kappa B Proteins medicine.symptom business medicine.drug |
| Zdroj: | Pancreatology. 16:477-488 |
| ISSN: | 1424-3903 |
| Popis: | The incidence of acute pancreatitis (AP) is increasing globally and mortality could be high among patients with organ failure and infected necrosis. The predominant factors responsible for the morbidity and mortality of AP are systemic inflammatory response syndrome and multiorgan dysfunction. Even though preclinical studies have shown antisecretory agents (somatostatin), antioxidants (S-adenosyl methionine [SAM], selenium), protease inhibitors, platelet activating factor inhibitor (Lexipafant), and anti-inflammatory immunomodulators (eg. prostaglandin E, indomethacin) to benefit AP in terms of reducing the severity and/or mortality, most of these agents have shown heterogeneous results in clinical studies. Several years of experimental studies have implicated nuclear factor-kappa B (NF-κB) activation as an early and central event in the progression of inflammation in AP. In this manuscript, we review the literature on the role of NF-κB in the pathogenesis of AP, its early intraacinar activation, and how it results in progression of the disease. We also discuss why anti-protease, antisecretory, and anti-inflammatory agents are unlikely to be effective in clinical acute pancreatitis. NF-κB, being a central molecule that links the initial acinar injury to systemic inflammation and perpetuate the inflammation, we propose that more studies be focussed towards targeted inhibition of NF-κB activity. Direct NF-κB inhibition strategies have already been attempted in patients with various cancers. So far, peroxisome proliferator activator receptor gamma (PPAR-γ) ligand, pyrrolidine dithiocarbamate (PDTC), proteasome inhibitor and calpain I inhibitor have been shown to have direct inhibitory effects on NF-κB activation in experimental AP. |
| Databáze: | OpenAIRE |
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