title: Local and Systemic IKKε and NF-κB Signaling Associated with Sjögren's Syndrome Immunopathogenesis.
abstract: 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.
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China.
authors.forename: Weiqian
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Cao
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China.
authors.forename: Danyi
authors.initials: D
authors.lastname: Xu
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Xu
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China.
authors.forename: Liqin
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China.
authors.forename: Lihuan
authors.initials: L
authors.lastname: Yue
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China.
authors.forename: Chuanyin
authors.initials: C
authors.lastname: Sun
authors.affiliation: Department of Chinese Internal Medicine, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China.
authors.forename: Guolin
authors.initials: G
authors.lastname: Wu
authors.affiliation: Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Qian
mesh_terms: D000328:Adult; D001706:Biopsy; D015331:Cohort Studies; D004848:Epithelium / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D012859:Sjogren's Syndrome / Q000175:diagnosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D012333:RNA, Messenger; D051550:I-kappa B Kinase