Back to Search Start Over

Evidence for the involvement of mTOR inhibition and basal autophagy in familial Mediterranean fever phenotype

Authors :
Ioannis Mitroulis
Konstantinos Ritis
Konstantinos Kambas
Akrivi Chrysanthopoulou
Ioannis Kourtzelis
Source :
Human Immunology. 72:135-138
Publication Year :
2011
Publisher :
Elsevier BV, 2011.

Abstract

Familial Mediterranean fever (FMF) inflammatory attacks are often triggered by metabolic or physical stress. mTOR signaling and autophagy modulate cellular responses to metabolic danger signals. In this study, we investigated the implication of mTOR inhibition and autophagy in FMF pathophysiology. mTOR inhibition induced MEFV gene expression in polymorphonuclear cells (PMNs) from healthy individuals, whereas it had no effect on PMNs from attack-free FMF patients. A significant reduction in pyrin levels in PMNs from FMF patients after mTOR inhibition was also observed. Pyrin levels in control PMNs remained unaffected. Moreover, the basal autophagic status in PMNs from FMF patients was reduced, as indicated by the lower LC3B-II/I ratio and ATG mRNA expression levels. However, mTOR inhibition had similar effects on the induction of autophagy in the two groups. The differential pyrin expression after metabolic stress induction and the impaired basal autophagy suggest a potential role in the triggering of FMF attacks.

Details

ISSN :
01988859
Volume :
72
Database :
OpenAIRE
Journal :
Human Immunology
Accession number :
edsair.doi.dedup.....3d7012aa3e4066260863705e1f0f0203
Full Text :
https://doi.org/10.1016/j.humimm.2010.11.006