Academic Journal
HLA–B27 modulates nuclear factor κB activation in human monocytic cells exposed to lipopolysaccharide
| العنوان: | HLA–B27 modulates nuclear factor κB activation in human monocytic cells exposed to lipopolysaccharide |
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| المؤلفون: | Penttinen, Markus A., Holmberg, Carina I., Sistonen, Lea, Granfors, Kaisa |
| المصدر: | Arthritis & Rheumatism ; volume 46, issue 8, page 2172-2180 ; ISSN 0004-3591 1529-0131 |
| بيانات النشر: | Wiley |
| سنة النشر: | 2002 |
| المجموعة: | Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: | Objective To study whether HLA–B27 modifies some key factors controlling inflammatory responses on lipopolysaccharide (LPS) stimulation in human monocytic cells. Methods U937 human monocytic cells were stably transfected with either HLA–B27 genomic DNA, HLA–B27 complementary DNA, HLA–A2 genomic DNA, or with the resistant vector pSV2neo (mock) alone. The cells were stimulated with LPS. Electrophoretic mobility shift assay was performed to determine nuclear factor κB (NF‐κB) and heat‐shock factor 1 activities, Western blotting was performed to detect the expressions of inhibitory κBα (IκBα) and heat‐shock proteins (HSPs), and enzyme‐linked immunosorbent assay was performed to measure tumor necrosis factor α (TNFα) secretion. Results The expression of HLA–B27 modulated the response to LPS in U937 human monocytic cells. Stimulation with LPS led to faster degradation of IκBα regulatory proteins, accompanied by faster and prolonged activation of NF‐κB in HLA–B27–expressing cells compared with HLA–A2 and mock transfectants. The secretion of TNFα upon LPS stimulation correlated well with the activation of NF‐κB. No activation of the heat‐shock response was observed. Conclusion Our data indicate that HLA–B27 has effects on host responses to LPS that are unrelated to antigen presentation. Two crucial events in the development of arthritis, the activation of NF‐κB and the secretion of TNFα, were found to be enhanced in HLA–B27–expressing cells upon LPS stimulation. Because LPS is known to be present in the inflamed joints of patients with reactive arthritis (ReA), the enhanced inflammatory response of HLA–B27–positive cells upon LPS stimulation offers an attractive explanation for the role of HLA–B27 in the development of ReA. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1002/art.10557 |
| الاتاحة: | http://dx.doi.org/10.1002/art.10557 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fart.10557 https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.10557 |
| Rights: | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| رقم الانضمام: | edsbas.B7ED17A4 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1002/art.10557 |
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