Local and Systemic IKKepsilon and NF-kappaB Signaling Associated with Sjogren's Syndrome Immunopathogenesis.

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