Novel NLRP3/cryopyrin mutations and pro-inflammatory cytokine profiles in Behçet's syndrome patients
| Autor: | Yetis Gultekin, Elif Eren, Sahru Yuksel, Duygu Demiröz, Izzet Fresko, Ali Can Sahillioglu, Nesrin Özören, Gulen Hatemi, Cezmi A. Akdis |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Adult
Lipopolysaccharides Male Turkey medicine.medical_treatment Immunology DNA Mutational Analysis Interleukin-1beta medicine.disease_cause Pyrin domain Pathogenesis Young Adult NLR Family Pyrin Domain-Containing 3 Protein medicine Immunology and Allergy Humans Genetic Predisposition to Disease Cells Cultured Mutation Polymorphism Genetic integumentary system business.industry Tumor Necrosis Factor-alpha Behcet Syndrome Inflammasome General Medicine Acquired immune system CARD Signaling Adaptor Proteins Cytoskeletal Proteins Cytokine Cytokine secretion Tumor necrosis factor alpha Female Inflammation Mediators business Carrier Proteins medicine.drug |
| Popis: | Behçet’s syndrome (BS) is a systemic inflammatory disorder with unknown etiology. Features of both innate and adaptive immunity have been claimed in the pathogenesis of BS. To test the possible dysregulation of the NLRP3/cryopyrin (Nod-like receptor with a pyrin domain 3) inflammasome, as a result of mutation(s), we performed single-strand conformation polymorphism analyses and/or sequencing of all the coding regions and intron–exon boundaries of NLRP3/cryopyrin and ASC (apoptosis-associated speck-like protein containing CARD) genes from Turkish BS patients and healthy controls. At the same time, we determined pro-inflammatory cytokine secretion profiles of peripheral blood cells in response to LPS treatment using ELISA. BS patients with vascular involvement showed significantly increased levels of TNF-α release at 2-, 4- and 8-h post-treatment and significantly increased IL-1β levels were detected at 2h (P = 0.005) and 4h (P = 0.025) (n = 10). We identified four mutations in the NLRP3/cryopyrin gene, V200M (n = 3/104) and T195M (n = 1/104), in BS patients but none in control samples. No mutations were detected in the ASC gene. The effect of these NLRP3/cryopyrin mutants on ASC speck assembly and IL-1β secretion was tested and the V200M mutant was shown to induce IL-1β secretion. Thus, it is likely that certain mutations in NLRP3/cryopyrin in combination with yet unknown other factors may contribute to the pro-inflammatory cytokine profiles in BS patients. |
| Databáze: | OpenAIRE |
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