Back to Search
Start Over
Dysregulated production of interleukin-1β upon activation of the NLRP3 inflammasome in patients with familial Mediterranean fever.
- Source :
-
Human Immunology . Jul2015, Vol. 76 Issue 7, p488-495. 8p. - Publication Year :
- 2015
-
Abstract
- Familial Mediterranean fever (FMF) is caused by mutations in pyrin, a protein expressed in innate immune cells that interacts with caspase-1 and other inflammasome components to regulate interleukin (IL)-1β maturation. Since NLRP3 inflammasome represents major source of IL-1β, we studied its protein expression and function in FMF. We isolated peripheral white blood cells (WBCs) from 20 symptoms-free FMF patients and 21 healthy individuals. Intracellular protein expression of NLRP3, caspase-1, IL-1β at baseline and after LPS/ATP sequential treatment for NLRP3 activation was assessed by immunoblotting. Secreted IL-1β was quantified by ELISA. THP-1 cells were transfected with wild-type or mutant pyrin and IL-1β secretion was measured. FMF WBCs exhibited lower NLRP3 and active caspase-1 protein expression compared to healthy individuals, and LPS/ATP treatment resulted in significantly lower intracellular IL-1β levels in FMF patients. Likewise, LPS/ATP induced caspase-1-dependent IL-1β release at significantly lower amounts in the FMF group (1182 ± 192 versus 2134 ± 245 pg/mL in controls, p = 0.004). Consistently, THP-1 cells transfected with FMF-associated M694V mutant pyrin displayed lower LPS/ATP-induced IL-1β compared with wild-type pyrin-transfected cells. FMF WBCs demonstrate reduced NLRP3-mediated IL-1β production. Additional studies are needed to define whether this finding represents a compensatory mechanism to control inflammation or is directly linked to disease pathogenesis. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01988859
- Volume :
- 76
- Issue :
- 7
- Database :
- Academic Search Index
- Journal :
- Human Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 103552806
- Full Text :
- https://doi.org/10.1016/j.humimm.2015.06.007