| Ankylosing spondylitis macrophage production of higher levels of interleukin-23 in response to lipopolysaccharide without induction of a significant unfolded protein response. | |
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MedLine Citation:
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PMID: 22127699 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: Previous studies of the HLA-B27-transgenic rat model of ankylosing spondylitis (AS) suggested that macrophages develop an intracellular stress response called the unfolded protein response (UPR) and, as a result, secrete increased amounts of cytokines in response to Toll-like receptor agonists such as lipopolysaccharide (LPS). Our objective was to determine whether macrophages from AS patients also undergo a UPR and secrete increased cytokines/chemokines in response to LPS. METHODS: Peripheral blood monocytes isolated from 10 AS patients and 10 healthy controls were differentiated in vitro with macrophage colony-stimulating factor. Select samples were treated with interferon-γ (IFNγ) to up-regulate class I major histocompatibility complex (HLA-B) expression prior to stimulation with LPS for either 3 hours (for RNA) or 8-24 hours (for supernatant). UPR induction was assessed by measuring the expression of messenger RNA for ERdj4, BiP, and CCAAT/enhancer binding protein homologous protein 10 (CHOP). RESULTS: Although IFNγ treatment up-regulated HLA-B expression (2-fold; P < 0.0001), neither IFNγ nor LPS substantially enhanced BiP or CHOP expression (<1.3-fold). ERdj4 expression increased weakly, but not significantly, in AS samples treated with IFNγ plus LPS (2.2-fold; P = 0.31). In response to LPS, AS macrophages secreted more CXCL9, interleukin-10 (IL-10), IL-12p70, IL-23, and tumor necrosis factor α than did control macrophages (P ≤ 0.025). The most striking difference was observed for IL-23 (median 265 pg/ml in AS patients versus 9 pg/ml in controls; P = 0.0007). We did not detect significant differences in IL-6, IL-8, or IFNβ production. CONCLUSION: The greater production of IL-23 by AS patient macrophages in response to LPS provides further support for the development of Th17/IL-23-directed therapy. Since significant UPR induction was not detected in AS patient macrophages, the relationship between UPR and inflammatory cytokine production remains unclear. |
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Authors:
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Ling Zeng; Mary J Lindstrom; Judith A Smith |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Arthritis and rheumatism Volume: 63 ISSN: 1529-0131 ISO Abbreviation: Arthritis Rheum. Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-11-30 Completed Date: 2012-01-27 Revised Date: 2012-04-25 |
Medline Journal Info:
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Nlm Unique ID: 0370605 Medline TA: Arthritis Rheum Country: United States |
Other Details:
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Languages: eng Pagination: 3807-17 Citation Subset: AIM; IM |
Copyright Information:
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Copyright © 2011 by the American College of Rheumatology. |
Affiliation:
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University of Wisconsin Madison, School of Medicine and Public Health, Madison, WI 53792-4108, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult CCAAT-Enhancer-Binding Proteins / metabolism Case-Control Studies Cells, Cultured Chemokines / metabolism Cytokines / metabolism Female HLA-B Antigens / metabolism Humans Interferon-gamma / pharmacology Interleukin-23 / metabolism* Lipopolysaccharides / pharmacology* Macrophages / drug effects*, metabolism*, pathology Male Middle Aged Oligopeptides / metabolism Spondylitis, Ankylosing / metabolism*, pathology Transcription Factor CHOP / metabolism Unfolded Protein Response / drug effects*, physiology Young Adult |
| Grant Support | |
ID/Acronym/Agency:
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1UL1RR02501/RR/NCRR NIH HHS; 1UL1RR025011/RR/NCRR NIH HHS; AI081045/AI/NIAID NIH HHS; K08 AI081045-01/AI/NIAID NIH HHS; K08 AI081045-02/AI/NIAID NIH HHS; K08 AI081045-03/AI/NIAID NIH HHS; UL1 RR025011-01/RR/NCRR NIH HHS; UL1 RR025011-02/RR/NCRR NIH HHS; UL1 RR025011-03/RR/NCRR NIH HHS; UL1 RR025011-04/RR/NCRR NIH HHS; UL1 RR025011-05/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Bax-inhibiting peptide, BIP; 0/CCAAT-Enhancer-Binding Proteins; 0/Chemokines; 0/Cytokines; 0/DDIT3 protein, human; 0/HLA-B Antigens; 0/Interleukin-23; 0/Lipopolysaccharides; 0/Oligopeptides; 147336-12-7/Transcription Factor CHOP; 82115-62-6/Interferon-gamma |
| Comments/Corrections | |
Comment In:
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Arthritis Rheum. 2011 Dec;63(12):3668-71
[PMID:
22127689
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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