Increased expression of the NLRP3 inflammasome components in patients with Behçet's disease.

En Hyung Kim,Sun Park,Eun-So Lee,Mi-Jin Park

doi:10.1186/s12950-015-0086-z

Abstract

BackgroundBehçet’s disease (BD) is a systemic inflammatory disease with manifestations including recurrent oral and genital ulcerations, and vasculitis involving the skin, mucosa, joints, eyes, veins, arteries, nervous and gastrointestinal systems. BD is seen as a disease at the crossroad between autoimmune and autoinflammatory syndromes, possibly triggered by an aberrant response to infectious stimuli. The relevance of Gram negative bacteria-mediated oral inflammation with the increased expression of NACHT, LRR, and PYD domains-containing protein 3 (NLRP3), leading to systemic inflammation, prompted us to investigate the expression of NLRP3 inflammasome components and its link with IL-1β hypersecretion.FindingsWhen peripheral blood mononuclear cells (PBMCs) from 15 active, 15 stable BD patients and 15 healthy volunteers were stimulated, the basal and LPS-induced expressions of NLRP3 inflammasome components were significantly increased at both mRNA and protein levels in BD patients compared to healthy controls. Also, increased expression of NLRP3 and ASC was observed in 25 BD skin lesions compared to 25 erythema nodosum patients. Compatible with this, secretion of IL-1β by PBMCs stimulated with LPS alone or LPS plus ATP was increased in BD compared to healthy controls, which was suppressed by caspase-1 inhibitor.ConclusionOur findings suggest the possible link between increased IL-1β secretion and increased expression of NLRP3 inflammasome components in BD patients with skin manifestations.Electronic supplementary materialThe online version of this article (doi:10.1186/s12950-015-0086-z) contains supplementary material, which is available to authorized users.

Highlights

Behçet’s disease (BD) is a systemic inflammatory disease with manifestations including recurrent oral and genital ulcerations, and vasculitis involving the skin, mucosa, joints, eyes, veins, arteries, nervous and gastrointestinal systems
Our findings suggest the possible link between increased IL-1β secretion and increased expression of NLRP3 inflammasome components in BD patients with skin manifestations
These findings show that mRNA and protein levels of NLRP3 inflammasome components are increased in BD patients

Summary

Introduction

Behçet’s disease (BD) is a systemic inflammatory disease with manifestations including recurrent oral and genital ulcerations, and vasculitis involving the skin, mucosa, joints, eyes, veins, arteries, nervous and gastrointestinal systems. Oral microbial flora have long been implicated in the pathogenesis of BD [2]. It is not clear how infection induces an immune response and initiates the development of BD. It was shown that NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome is upregulated when infected by. As oral ulcer precede BD for many years and EN like lesions, one of most common skin manifestions in BD, which are characterized by septal and lobular panniculitis and most importantly vasculitis, we investigated whether NLRP3 inflammasome expression is increased at the mRNA and protein levels in BD patients with skin manifestations. We studied whether IL-1β production was mediated through NLRP3 inflammasome dependent pathway in BD

Methods

Results and discussion

Conclusion