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

• Published in: Clinical immunology (Orlando, Fla.) Vol. 161; no. 2; pp. 300 - 307
• Main Authors: Hofmann, S.R, Kubasch, A.S, Ioannidis, C, Rösen-Wolff, A, Girschick, H.J, Morbach, H, Hedrich, C.M
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2015
• Subjects: Allergy and Immunology; Bone; Carrier Proteins - metabolism; Cell Line, Tumor; Cells, Cultured; Child; CNO; CRMO; Cytokine; DNA Methylation; Enzyme-Linked Immunosorbent Assay; Extracellular Signal-Regulated MAP Kinases - metabolism; Flow Cytometry; Gene Expression; Humans; IL-10; Inflammasome; Inflammasomes - metabolism; Inflammation; Interleukin-10 - genetics; Interleukin-10 - metabolism; Interleukin-1beta - genetics; Interleukin-1beta - metabolism; Interleukins - genetics; Interleukins - metabolism; Monocytes - metabolism; NLR Family, Pyrin Domain-Containing 3 Protein; Osteomyelitis - genetics; Osteomyelitis - metabolism; Osteomyelitis - pathology; Promoter Regions, Genetic - genetics; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; Sp1 Transcription Factor - genetics; Sp1 Transcription Factor - metabolism; CNO; Cytokine; Inflammation; Inflammasome; Bone; IL-10; CRMO
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2015.09.013

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.