title: Evidence for the involvement of mTOR inhibition and basal autophagy in familial Mediterranean fever phenotype.
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.
authors.affiliation: First Department of Internal Medicine, Democritus University of Thrace, Alexandroupolis, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Mitroulis
authors.forename: Ioannis
authors.initials: I
authors.lastname: Kourtzelis
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Kambas
authors.forename: Akrivi
authors.initials: A
authors.lastname: Chrysanthopoulou
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Ritis
mesh_terms: D001343:Autophagy / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D003546:Cysteine Endopeptidases / Q000276:immunology / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D010505:Familial Mediterranean Fever / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D009154:Mutation / Q000276:immunology; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D010641:Phenotype; D000071198:Pyrin; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D020123:Sirolimus / Q000494:pharmacology*; D013312:Stress, Physiological / Q000187:drug effects / Q000276:immunology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; D000071198:Pyrin; D012333:RNA, Messenger; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D003546:Cysteine Endopeptidases; D020123:Sirolimus