دورية أكاديمية
أعرض في EDS

Disruption of macrophage pro-inflammatory cytokine release in Crohn's disease is associated with reduced optineurin expression in a subset of patients.

التفاصيل البيبلوغرافية
العنوان: Disruption of macrophage pro-inflammatory cytokine release in Crohn's disease is associated with reduced optineurin expression in a subset of patients.
المؤلفون: Smith AM; Microbial Diseases, Eastman Dental Institute, University College London, London, UK., Sewell GW, Levine AP, Chew TS, Dunne J, O'Shea NR, Smith PJ, Harrison PJ, Macdonald CM, Bloom SL, Segal AW
المصدر: Immunology [Immunology] 2015 Jan; Vol. 144 (1), pp. 45-55.
نوع المنشور: Clinical Trial; Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Blackwell Scientific Publications Country of Publication: England NLM ID: 0374672 Publication Model: Print Cited Medium: Internet ISSN: 1365-2567 (Electronic) Linking ISSN: 00192805 NLM ISO Abbreviation: Immunology Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Oxford : Blackwell Scientific Publications
مواضيع طبية MeSH: Crohn Disease/*immunology , Cytokines/*immunology , Gene Expression Regulation/*immunology , Macrophages/*immunology , Transcription Factor TFIIIA/*immunology, Adult ; Cell Cycle Proteins ; Cell Line, Tumor ; Crohn Disease/pathology ; Female ; Humans ; Inflammation/immunology ; Inflammation/pathology ; Macrophages/pathology ; Male ; Membrane Transport Proteins ; Middle Aged
مستخلص: Crohn's disease (CD) is a complex and highly heterogeneous chronic inflammatory disorder, primarily affecting the gastrointestinal tract. Genetic and functional studies have highlighted a key role for innate immunity in its pathogenesis. Profound systemic defects in innate immunity and acute inflammation are understood to result in markedly delayed clearance of bacteria from the tissues, leading to local chronic granulomatous inflammation and compensatory adaptive immunological changes. Macrophages, key orchestrators of acute inflammation, are likely to play an important role in the initial impaired innate immune response. Monocyte-derived macrophages from CD patients stimulated with Escherichia coli were shown to release attenuated levels of tumour necrosis factor and interferon-γ with normal secretion of interleukin-8 (IL-8), IL-10 and IL-6. In controls, the secretion of these cytokines was strongly positively correlated, which was not seen with CD macrophages. The transcriptomes of CD and control macrophages were examined in an attempt to understand the molecular basis of this defect. 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. The most common of these was optineurin (OPTN) which was under-expressed in approximately 10% of the 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.
(© 2014 The Authors. Immunology published by John Wiley & Sons Ltd., Immunology.)
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معلومات مُعتمدة: United Kingdom WT_ Wellcome Trust; G0902005 United Kingdom MRC_ Medical Research Council; G0902022 United Kingdom MRC_ Medical Research Council; MR/L000261/1 United Kingdom MRC_ Medical Research Council
فهرسة مساهمة: Keywords: cytokine; gene expression; immunodeficiency; inflammation; inflammatory bowel disease
المشرفين على المادة: 0 (Cell Cycle Proteins)
0 (Cytokines)
0 (Membrane Transport Proteins)
0 (OPTN protein, human)
0 (Transcription Factor TFIIIA)
تواريخ الأحداث: Date Created: 20140620 Date Completed: 20150210 Latest Revision: 20240706
رمز التحديث: 20240706
مُعرف محوري في PubMed: PMC4264909
DOI: 10.1111/imm.12338
PMID: 24943399
قاعدة البيانات: MEDLINE
الوصف
تدمد:1365-2567
DOI:10.1111/imm.12338