Disruption of macrophage pro-inflammatory cytokine release in Crohn's disease is associated with reduced optineurin expression in a subset of patients.
Bottom Line: There were no differentially expressed genes identified between the two groups, consistent with genetic heterogeneity; however, a number of molecules were found to be under-expressed in subgroups of CD patients.Reduced OPTN expression coincided with lower intracellular protein levels and diminished cytokine secretion after bacterial stimulation both in the patients and with small interfering RNA knockdown in THP-1 cells.Identifying and studying subgroups of patients with shared defective gene expression could aid our understanding of the mechanisms underlying highly heterogeneous diseases such as CD.
Affiliation: Microbial Diseases, Eastman Dental Institute, University College London, London, UK.Show MeSH
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Mentions: Given the important roles of TNF-α, IFN-γ, IL-6, IL-8 and IL-10 in acute inflammation and the previous association of these cytokines with CD, we determined their secretion by macrophages over a 24-hr period of stimulation with HkEc. The secretion of TNF-α (P = 0·0045) and IFN-γ (P = 0·0004) were significantly lower in the CD cohort (n = 43) compared with the HC (n = 39) (Fig.1a,b) whereas equivalent amounts of IL-6, IL-8 and IL-10 were released in the two groups (Fig.1c–e).
Affiliation: Microbial Diseases, Eastman Dental Institute, University College London, London, UK.