Document Detail


Pathogenic mechanisms of acute pancreatitis.
MedLine Citation:
PMID:  22885948     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE OF REVIEW: In this article, recent advances in the pathogenesis of acute pancreatitis have been reviewed.
RECENT FINDINGS: Pathologic intra-acinar trypsinogen activation had been hypothesized to be the central mechanism of pancreatitis for over a century. This hypothesis could be explored for the first time with the development of a novel mouse model lacking pathologic intra-acinar trypsinogen activation. It became clear that intra-acinar trypsinogen activation contributes to early acinar injury, but local and systemic inflammation progress independently during pancreatitis. Early intra-acinar nuclear factor kappa B (NFκB) activation, which occurs parallel to but independent of trypsinogen activation, may be crucial in pancreatitis. Although the mechanism of NFκB and trypsinogen activation is not entirely clear, further insights have been made into key pathogenic cellular events such as calcium signaling, mitochondrial dysfunction, endoplasmic reticulum (ER) stress, autophagy and impaired trafficking, and lysosomal and secretory responses. Cellular intrinsic damage-sensing mechanisms that lead to activation of the inflammatory response aimed at repair, but lead to disease when overwhelmed, are beginning to be understood.
SUMMARY: New findings necessitate a paradigm shift in our understanding of acute pancreatitis. Intra-acinar trypsinogen activation leads to early pancreatic injury, but the inflammatory response of acute pancreatitis develops independently, driven by early activation of inflammatory pathways.
Authors:
Raghuwansh P Sah; Pramod Garg; Ashok K Saluja
Related Documents :
22725668 - A review of the molecular aspects of melatonin's anti-inflammatory actions: recent insi...
10933938 - Role of vector in activation of t cell subsets in immune responses against the secreted...
22556158 - The role of cyclooxygenase-2 in mechanical ventilation-induced lung injury.
12631618 - Significant antitumoral activity of cationic multilamellar liposomes containing human i...
15720228 - Role of inflammatory mediators in angiogenesis.
23932568 - Systems biology of host-mycobiota interactions: dissecting dectin-1 and dectin-2 signal...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review    
Journal Detail:
Title:  Current opinion in gastroenterology     Volume:  28     ISSN:  1531-7056     ISO Abbreviation:  Curr. Opin. Gastroenterol.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-08-13     Completed Date:  2013-02-06     Revised Date:  2013-09-03    
Medline Journal Info:
Nlm Unique ID:  8506887     Medline TA:  Curr Opin Gastroenterol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  507-15     Citation Subset:  IM    
Affiliation:
Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Acinar Cells / metabolism
Animals
Autophagy
Calcium / metabolism
Humans
Inflammasomes
Mitochondria / physiology
NF-kappa B / metabolism*
Pancreatitis / enzymology*,  metabolism
Trypsinogen / metabolism*
Grant Support
ID/Acronym/Agency:
R01 DK058694/DK/NIDDK NIH HHS; R01 DK058694/DK/NIDDK NIH HHS; R01 DK092145/DK/NIDDK NIH HHS; R01 DK092145/DK/NIDDK NIH HHS; R01 DK093047/DK/NIDDK NIH HHS; R01 DK093047/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Inflammasomes; 0/NF-kappa B; 7440-70-2/Calcium; 9002-08-8/Trypsinogen
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Genetics of alcoholic and nonalcoholic pancreatitis.
Next Document:  Relationship between inflammatory markers, oxidant-antioxidant status and intima-media thickness in ...