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Clin Immunol. 2015 Dec;161(2):300-7. doi: 10.1016/j.clim.2015.09.013. Epub 2015 Sep 25.

Altered expression of IL-10 family cytokines in monocytes from CRMO patients result in enhanced IL-1β expression and release.

Author information

1
Pediatric Rheumatology and Immunology, Children's Hospital, Universitätsklinikum Carl Gustav Carus, TU Dresden, Dresden, Germany.
2
Division of Rheumatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
3
Vivantes Klinikum Friedrichshain, Children's Hospital, Berlin, Germany.
4
Pediatric Rheumatology and Immunology, Children's Hospital, University of Würzburg, Würzburg, Germany.
5
Pediatric Rheumatology and Immunology, Children's Hospital, Universitätsklinikum Carl Gustav Carus, TU Dresden, Dresden, Germany; Division of Rheumatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. Electronic address: Christian.hedrich@uniklinikum-dresden.de.

Abstract

Chronic recurrent multifocal osteomyelitis (CRMO) is characterized by reduced activation of protein kinases ERK1 and 2 in monocytes resulting in impaired IL-10 expression. IL10 and its homologs IL19 and IL20 are organized in the IL10 cluster on chromosome 1q32. IL-10 and IL-19 are immune-regulatory cytokines, while IL-20 acts in a pro-inflammatory manner. The NLRP3 inflammasome, a multi-protein complex forming in response to innate stimuli, mediates IL-1β cleavage and release. Here, we investigated IL-10-related cytokine expression in CRMO monocytes, underlying molecular events, and effects on inflammatory responses. We observed reduced anti-inflammatory IL-10 and IL-19 expression, and enhanced IL-20 expression in CRMO monocytes. Reduced IL-10 and IL-19 expression was associated with impaired Sp-1 recruitment to regulatory regions, contributing to NLRP3 inflammasome activation, which may induce inflammatory bone-loss. Our findings underscore the importance of balanced receptor-, cell-, and tissue-specific cytokine expression for immune homeostasis, providing additional arguments for cytokine blocking strategies in CRMO.

KEYWORDS:

Bone; CNO; CRMO; Cytokine; IL-10; Inflammasome; Inflammation

PMID:
26404542
DOI:
10.1016/j.clim.2015.09.013
[Indexed for MEDLINE]

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