Skip to main content
Top
Published in: Journal of Inflammation 1/2015

Open Access 01-12-2015 | Short Report

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

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

Published in: Journal of Inflammation | Issue 1/2015

Login to get access

Abstract

Background

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. 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.

Findings

When 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.

Conclusion

Our findings suggest the possible link between increased IL-1β secretion and increased expression of NLRP3 inflammasome components in BD patients with skin manifestations.
Appendix
Available only for authorised users
Literature
1.
go back to reference Direskeneli H. Autoimmunity vs autoinflammation in Behcet’s disease: do we oversimplify a complex disorder? Rheumatology (Oxford). 2006;45:1461–5.CrossRef Direskeneli H. Autoimmunity vs autoinflammation in Behcet’s disease: do we oversimplify a complex disorder? Rheumatology (Oxford). 2006;45:1461–5.CrossRef
2.
go back to reference Pineton de Chambrun M, Wechsler B, Geri G, Cacoub P, Saadoun D. New insights into the pathogenesis of Behcet’s disease. Autoimmun Rev. 2012;11:687–98.PubMedCrossRef Pineton de Chambrun M, Wechsler B, Geri G, Cacoub P, Saadoun D. New insights into the pathogenesis of Behcet’s disease. Autoimmun Rev. 2012;11:687–98.PubMedCrossRef
3.
go back to reference Yamaguchi Y, Kurita-Ochiai T, Kobayashi R, Suzuki T, Ando T. Activation of the NLRP3 inflammasome in Porphyromonas gingivalis-accelerated atherosclerosis. Pathog Dis. 2015;73:epub. doi:10.1093/femspd/ftv011.CrossRef Yamaguchi Y, Kurita-Ochiai T, Kobayashi R, Suzuki T, Ando T. Activation of the NLRP3 inflammasome in Porphyromonas gingivalis-accelerated atherosclerosis. Pathog Dis. 2015;73:epub. doi:10.​1093/​femspd/​ftv011.CrossRef
4.
go back to reference Liang L, Tan X, Zhou Q, Zhu Y, Tian Y, Yu H, et al. IL-1beta triggered by peptidoglycan and lipopolysaccharide through TLR2/4 and ROS-NLRP3 inflammasome-dependent pathways is involved in ocular Behcet’s disease. Invest Ophthalmol Vis Sci. 2013;54:402–14.PubMedCrossRef Liang L, Tan X, Zhou Q, Zhu Y, Tian Y, Yu H, et al. IL-1beta triggered by peptidoglycan and lipopolysaccharide through TLR2/4 and ROS-NLRP3 inflammasome-dependent pathways is involved in ocular Behcet’s disease. Invest Ophthalmol Vis Sci. 2013;54:402–14.PubMedCrossRef
5.
go back to reference Mitroulis I, Skendros P, Ritis K. Targeting IL-1beta in disease; the expanding role of NLRP3 inflammasome. Eur J Intern Med. 2010;21:157–63.PubMedCrossRef Mitroulis I, Skendros P, Ritis K. Targeting IL-1beta in disease; the expanding role of NLRP3 inflammasome. Eur J Intern Med. 2010;21:157–63.PubMedCrossRef
6.
go back to reference Qiao Y, Wang P, Qi J, Zhang L, Gao C. TLR-induced NF-kappaB activation regulates NLRP3 expression in murine macrophages. FEBS Lett. 2012;586:1022–6.PubMedCrossRef Qiao Y, Wang P, Qi J, Zhang L, Gao C. TLR-induced NF-kappaB activation regulates NLRP3 expression in murine macrophages. FEBS Lett. 2012;586:1022–6.PubMedCrossRef
7.
go back to reference Netea MG, Simon A, van de Veerdonk F, Kullberg BJ, Van der Meer JW, Joosten LA. IL-1beta processing in host defense: beyond the inflammasomes. PLoS Pathog. 2010;6, e1000661.PubMedCentralPubMedCrossRef Netea MG, Simon A, van de Veerdonk F, Kullberg BJ, Van der Meer JW, Joosten LA. IL-1beta processing in host defense: beyond the inflammasomes. PLoS Pathog. 2010;6, e1000661.PubMedCentralPubMedCrossRef
9.
go back to reference Gogus F, Fresko I, Elbir Y, Eksioglu-Demiralp E, Direskeneli H. Oxidative burst response to monosodium urate crystals in patients with Behcet’s syndrome. Clin Exp Rheumatol. 2005;23 Suppl 38:S81–5.PubMed Gogus F, Fresko I, Elbir Y, Eksioglu-Demiralp E, Direskeneli H. Oxidative burst response to monosodium urate crystals in patients with Behcet’s syndrome. Clin Exp Rheumatol. 2005;23 Suppl 38:S81–5.PubMed
10.
go back to reference Kaneko F, Oyama N, Nishibu A. Streptococcal infection in the pathogenesis of Behcet’s disease and clinical effects of minocycline on the disease symptoms. Yonsei Med J. 1997;38:444–54.PubMedCrossRef Kaneko F, Oyama N, Nishibu A. Streptococcal infection in the pathogenesis of Behcet’s disease and clinical effects of minocycline on the disease symptoms. Yonsei Med J. 1997;38:444–54.PubMedCrossRef
11.
go back to reference Calguneri M, Kiraz S, Ertenli I, Benekli M, Karaarslan Y, Celik I. The effect of prophylactic penicillin treatment on the course of arthritis episodes in patients with Behcet’s disease. A randomized clinical trial. Arthritis Rheum. 1996;39:2062–5.PubMedCrossRef Calguneri M, Kiraz S, Ertenli I, Benekli M, Karaarslan Y, Celik I. The effect of prophylactic penicillin treatment on the course of arthritis episodes in patients with Behcet’s disease. A randomized clinical trial. Arthritis Rheum. 1996;39:2062–5.PubMedCrossRef
12.
go back to reference Do JE, Kwon SY, Park S, Lee ES. Effects of vitamin D on expression of toll-like receptors of monocytes from patients with Behcet’s disease. Rheumatology (Oxford). 2008;47:840–8.CrossRef Do JE, Kwon SY, Park S, Lee ES. Effects of vitamin D on expression of toll-like receptors of monocytes from patients with Behcet’s disease. Rheumatology (Oxford). 2008;47:840–8.CrossRef
13.
go back to reference Dinarello CA. Immunological and inflammatory functions of the interleukin-1 family. Annu Rev Immunol. 2009;27:519–50.PubMedCrossRef Dinarello CA. Immunological and inflammatory functions of the interleukin-1 family. Annu Rev Immunol. 2009;27:519–50.PubMedCrossRef
14.
go back to reference Gul A, Tugal-Tutkun I, Dinarello CA, Reznikov L, Esen BA, Mirza A, et al. Interleukin-1beta-regulating antibody XOMA 052 (gevokizumab) in the treatment of acute exacerbations of resistant uveitis of Behcet’s disease: an open-label pilot study. Ann Rheum Dis. 2012;71:563–6.PubMedCrossRef Gul A, Tugal-Tutkun I, Dinarello CA, Reznikov L, Esen BA, Mirza A, et al. Interleukin-1beta-regulating antibody XOMA 052 (gevokizumab) in the treatment of acute exacerbations of resistant uveitis of Behcet’s disease: an open-label pilot study. Ann Rheum Dis. 2012;71:563–6.PubMedCrossRef
15.
go back to reference Keller M, Sollberger G, Beer HD. Thalidomide inhibits activation of caspase-1. J Immunol. 2009;183:5593–9.PubMedCrossRef Keller M, Sollberger G, Beer HD. Thalidomide inhibits activation of caspase-1. J Immunol. 2009;183:5593–9.PubMedCrossRef
Metadata
Title
Increased expression of the NLRP3 inflammasome components in patients with Behçet’s disease
Authors
En Hyung Kim
Mi-Jin Park
Sun Park
Eun-So Lee
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Journal of Inflammation / Issue 1/2015
Electronic ISSN: 1476-9255
DOI
https://doi.org/10.1186/s12950-015-0086-z

Other articles of this Issue 1/2015

Journal of Inflammation 1/2015 Go to the issue