Involvement of Substance P (SP) and Its Related NK1 Receptor in Primary Sjogren's Syndrome (pSS) Pathogenesis

Primary Sjogren's Syndrome (pSS) is a systemic autoimmune disease that primarily attacks the lacrimal and salivary glands, resulting in impaired secretory function characterized by xerostomia and xerophthalmia. Patients with pSS have been shown to have impaired salivary gland innervation and altered circulating levels of neuropeptides thought to be a cause of decreased salivation, including substance P (SP). Using Western blot analysis and immunofluorescence studies, we examined the expression levels of SP and its preferred G protein-coupled TK Receptor 1 (NK1R) and apoptosis markers in biopsies of the minor salivary gland (MSG) from pSS patients compared with patients with idiopathic sicca syndrome. We confirmed a quantitative decrease in the amount of SP in the MSG of pSS patients and demonstrated a significant increase in NK1R levels compared with sicca subjects, indicating the involvement of SP fibers and NK1R in the impaired salivary secretion observed in pSS patients. Moreover, the increase in apoptosis (PARP-1 cleavage) in pSS patients was shown to be related to JNK phosphorylation. Since there is no satisfactory therapy for the treatment of secretory hypofunction in pSS patients, the SP pathway may be a new potential diagnostic tool or therapeutic target.

Automated summary

Primary Sjogren's Syndrome (pSS) is an autoimmune disease that affects the lacrimal and salivary glands, resulting in reduced secretion and symptoms like dry mouth and dry eyes. This study found decreased levels of substance P (SP) and increased levels of NK1R in the minor salivary glands of pSS patients, suggesting their involvement in the impaired salivary secretion. The increase in apoptosis in pSS patients was also related to JNK phosphorylation.