Document Detail


Deficient autophagy unravels the ROS paradox in chronic granulomatous disease.
MedLine Citation:
PMID:  24879159     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Autophagy defects resulting in inflammation appear to be a key feature in the pathogenesis of Crohn colitis. An inflammatory colitis indistinguishable from Crohn disease is described in patients with chronic granulomatous disease (CGD). Patients with CGD have a mutated NADPH complex and are therefore deficient in reactive oxygen species (ROS) production; however, the underlying mechanism for the inflammatory colitis in CGD remained unknown. In a recent study, our group reported that NADPH-dependent ROS deficiency results in autophagic dysfunction that subsequently contributes to increased IL1B/interleukin 1β production. Mice deficient in the NADPH-complex component NCF4/p40phox, and CGD patients with a defect in NCF4 display minimal recruitment of LC3 to phagosomes in response to internalized bacteria and fungi. Human monocytes from patients with CGD with defective LC3 recruitment show increased IL1B production after LPS stimulation. Blocking IL1 protects NCF4-deficient mice from experimental colitis; importantly, improved clinical outcome in 2 CGD patients with colitis is also observed with IL1 blockade. Moreover, blocking IL1 restores defective autophagy in CGD mice and cells from patients with CGD. Thus, autophagic dysfunction underlies the pathogenesis of granulomatous colitis in CGD, and blocking IL1 can be used to treat CGD colitis.
Authors:
Frank L van de Veerdonk; Charles A Dinarello
Related Documents :
24150979 - Intraoperative dopamine release during globus pallidus internus stimulation in parkinso...
23992109 - Is the urinary biomarkers assessment a non-invasive approach to tubular lesions of the ...
23752339 - Correlation between plaque composition as assessed by virtual histology and c-reactive ...
10695939 - Effect of cigarette smoking on oral elastase activity in adult periodontitis patients.
23043129 - Health-related quality of life among patients with symptomatic carotid disease.
24050879 - Diagnostic value of real-time elastography in the assessment of hepatic fibrosis in pat...
12678399 - Pars plana vitrectomy in ocular behçet's disease.
6240069 - Autosomal dominant polycystic kidney disease: symptoms and clinical findings.
18181479 - Cardiac tamponade from slingshot metal darts in chuuk: a retrospective review of cases.
Publication Detail:
Type:  REVIEW    
Journal Detail:
Title:  Autophagy     Volume:  10     ISSN:  1554-8635     ISO Abbreviation:  Autophagy     Publication Date:  2014 Jun 
Date Detail:
Created Date:  2014-5-31     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101265188     Medline TA:  Autophagy     Country:  -    
Other Details:
Languages:  ENG     Pagination:  1141-1142     Citation Subset:  -    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

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


Previous Document:  Restarting stalled autophagy a potential therapeutic approach for the lipid storage disorder, Nieman...
Next Document:  A histone point mutation that switches on autophagy.