Local and Systemic IKKε and NF-κB Signaling Associated with Sjögren’s Syndrome Immunopathogenesis

The activated NF-κB signaling pathway plays an important role in pathogenesis of primary Sjögren’s syndrome (pSS). The inhibitor of κB (IκB) kinase (IKK) family such as IKKα, IKKβ, IKKγ, and IKKε, is required for this signaling. Our aim was to investigate the role of IKKα/β/γ/ε in patients with untr...

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Main Authors: Weiqian Chen, Jin Lin, Heng Cao, Danyi Xu, Bei Xu, Liqin Xu, Lihuan Yue, Chuanyin Sun, Guolin Wu, Wenbin Qian
Format: Article
Language:English
Published: Wiley 2015-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2015/534648
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author Weiqian Chen
Jin Lin
Heng Cao
Danyi Xu
Bei Xu
Liqin Xu
Lihuan Yue
Chuanyin Sun
Guolin Wu
Wenbin Qian
author_facet Weiqian Chen
Jin Lin
Heng Cao
Danyi Xu
Bei Xu
Liqin Xu
Lihuan Yue
Chuanyin Sun
Guolin Wu
Wenbin Qian
author_sort Weiqian Chen
collection DOAJ
description The activated NF-κB signaling pathway plays an important role in pathogenesis of primary Sjögren’s syndrome (pSS). The inhibitor of κB (IκB) kinase (IKK) family such as IKKα, IKKβ, IKKγ, and IKKε, is required for this signaling. Our aim was to investigate the role of IKKα/β/γ/ε in patients with untreated pSS. In minor salivary glands from pSS patients, phosphorylated IKKε (pIKKε), pIκBα, and pNF-κB p65 (p-p65) were highly expressed in ductal epithelium and infiltrating mononuclear cells by immunohistochemistry, compared to healthy individuals. pIKKα/β and pIKKγ were both negative. And pIKKε positively related to expression of p-p65. Furthermore, pIKKε and p-p65 expression significantly correlated with biopsy focus score and overall disease activity. Meanwhile, in peripheral blood mononuclear cells from pSS patients, pIKKε, total IKKε, pIKKα/β, and p-p65 were significantly increased by western blot, compared to healthy controls. However, there was no difference in IKKγ and IκBα between pSS patients and healthy individuals. These results demonstrated an abnormality of IKKε, IκBα, and NF-κB in pSS, suggesting a potential target of treatment for pSS based on the downregulation of IKKε expression and deregulation of NF-κB pathway.
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spelling doaj-art-07976094df864d84888d6bf8d7b10d6e2025-02-03T05:44:40ZengWileyJournal of Immunology Research2314-88612314-71562015-01-01201510.1155/2015/534648534648Local and Systemic IKKε and NF-κB Signaling Associated with Sjögren’s Syndrome ImmunopathogenesisWeiqian Chen0Jin Lin1Heng Cao2Danyi Xu3Bei Xu4Liqin Xu5Lihuan Yue6Chuanyin Sun7Guolin Wu8Wenbin Qian9Department of Rheumatology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, ChinaDepartment of Rheumatology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, ChinaDepartment of Rheumatology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, ChinaDepartment of Rheumatology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, ChinaDepartment of Rheumatology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, ChinaDepartment of Rheumatology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, ChinaDepartment of Rheumatology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, ChinaDepartment of Rheumatology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, ChinaDepartment of Chinese Internal Medicine, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, ChinaDepartment of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, ChinaThe activated NF-κB signaling pathway plays an important role in pathogenesis of primary Sjögren’s syndrome (pSS). The inhibitor of κB (IκB) kinase (IKK) family such as IKKα, IKKβ, IKKγ, and IKKε, is required for this signaling. Our aim was to investigate the role of IKKα/β/γ/ε in patients with untreated pSS. In minor salivary glands from pSS patients, phosphorylated IKKε (pIKKε), pIκBα, and pNF-κB p65 (p-p65) were highly expressed in ductal epithelium and infiltrating mononuclear cells by immunohistochemistry, compared to healthy individuals. pIKKα/β and pIKKγ were both negative. And pIKKε positively related to expression of p-p65. Furthermore, pIKKε and p-p65 expression significantly correlated with biopsy focus score and overall disease activity. Meanwhile, in peripheral blood mononuclear cells from pSS patients, pIKKε, total IKKε, pIKKα/β, and p-p65 were significantly increased by western blot, compared to healthy controls. However, there was no difference in IKKγ and IκBα between pSS patients and healthy individuals. These results demonstrated an abnormality of IKKε, IκBα, and NF-κB in pSS, suggesting a potential target of treatment for pSS based on the downregulation of IKKε expression and deregulation of NF-κB pathway.http://dx.doi.org/10.1155/2015/534648
spellingShingle Weiqian Chen
Jin Lin
Heng Cao
Danyi Xu
Bei Xu
Liqin Xu
Lihuan Yue
Chuanyin Sun
Guolin Wu
Wenbin Qian
Local and Systemic IKKε and NF-κB Signaling Associated with Sjögren’s Syndrome Immunopathogenesis
Journal of Immunology Research
title Local and Systemic IKKε and NF-κB Signaling Associated with Sjögren’s Syndrome Immunopathogenesis
title_full Local and Systemic IKKε and NF-κB Signaling Associated with Sjögren’s Syndrome Immunopathogenesis
title_fullStr Local and Systemic IKKε and NF-κB Signaling Associated with Sjögren’s Syndrome Immunopathogenesis
title_full_unstemmed Local and Systemic IKKε and NF-κB Signaling Associated with Sjögren’s Syndrome Immunopathogenesis
title_short Local and Systemic IKKε and NF-κB Signaling Associated with Sjögren’s Syndrome Immunopathogenesis
title_sort local and systemic ikkε and nf κb signaling associated with sjogren s syndrome immunopathogenesis
url http://dx.doi.org/10.1155/2015/534648
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