Local and systemic IKKζ and NF-κB signaling associated with Sjogren's syndrome immunopathogenesis

The activated NF-κB signaling pathway plays an important role in pathogenesis of primary Sjogren's syndrome (pSS). The inhibitor of κB (IκB) kinase (IKK) family such as IKKα, IKKβ, IKKγ, and IKKζ, is required for this signaling. Our aim was to investigate the role of IKKα/β/γ/ζ in patients with untreated pSS. In minor salivary glands from pSS patients, phosphorylated IKKζ (pIKKζ), 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 pIKKζ positively related to expression of p-p65. Furthermore, pIKKζ and p-p65 expression significantly correlated with biopsy focus score and overall disease activity. Meanwhile, in peripheral blood mononuclear cells from pSS patients, pIKKζ, total IKKζ, 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 IKKζ, IκBα, and NF-κB in pSS, suggesting a potential target of treatment for pSS based on the downregulation of IKKζ expression and deregulation of NF-κB pathway.