Local and Systemic IKKε and NF-κB Signaling Associated with Sjogren's Syndrome Immunopathogenesis

The activated NF-kappa B signaling pathway plays an important role in pathogenesis of primary Sjogren's syndrome (pSS). The inhibitor of kappa B (I kappa B) kinase (IKK) family such as IKK alpha, IKK beta, IKK gamma, and IKK epsilon, is required for this signaling. Our aim was to investigate the role of IKK alpha/beta/gamma/epsilon in patients with untreated pSS. In minor salivary glands from pSS patients, phosphorylated IKK epsilon (pIKK epsilon), pI kappa B alpha, and pNF-kappa B p65 (p-p65) were highly expressed in ductal epithelium and infiltrating mononuclear cells by immunohistochemistry, compared to healthy individuals. pIKK alpha/beta and pIKK gamma were both negative. And pIKK epsilon positively related to expression of p-p65. Furthermore, pIKK epsilon and p-p65 expression significantly correlated with biopsy focus score and overall disease activity. Meanwhile, in peripheral blood mononuclear cells from pSS patients, pIKK epsilon, total IKK epsilon, pIKK alpha/beta, and p-p65 were significantly increased by western blot, compared to healthy controls. However, there was no difference in IKK epsilon and I kappa B alpha between pSS patients and healthy individuals. These results demonstrated an abnormality of IKK epsilon, I kappa B alpha, and NF-kappa B in pSS, suggesting a potential target of treatment for pSS based on the downregulation of IKK epsilon expression and deregulation of NF-kappa B pathway.