Involvement of Substance P (SP) and Its Related NK1 Receptor in Primary Sjögren’s Syndrome (pSS) Pathogenesis
Pamela Rosso,
Elena Fico,
Serena Colafrancesco,
Mario Giuseppe Bellizzi,
Roberta Priori,
Bruna Cerbelli,
Martina Leopizzi,
Carla Giordano,
Antonio Greco,
Paola Tirassa,
Cinzia Severini,
Massimo Fusconi
Affiliations
Pamela Rosso
Institute of Biochemistry and Cell Biology, National Research Council (IBBC-CNR), Department of Sense Organs, Sapienza University of Rome, Viale del Policlinico 155, 00185 Rome, Italy
Elena Fico
Institute of Biochemistry and Cell Biology, National Research Council (IBBC-CNR), Department of Sense Organs, Sapienza University of Rome, Viale del Policlinico 155, 00185 Rome, Italy
Serena Colafrancesco
Department of Internal Medicine and Medical Specialties, Rheumatology Unit, Sapienza University of Rome, Viale del Policlinico 155, 00185 Rome, Italy
Mario Giuseppe Bellizzi
Department of Sense Organs, Sapienza University of Rome, Viale del Policlinico 155, 00185 Rome, Italy
Roberta Priori
Division of Rheumatology, Department of Clinical Internal, Anaesthesiologic and Cardiovascular Sciences, Sapienza University, Viale del Policlinico 155, 00185 Rome, Italy
Bruna Cerbelli
Department of Medico-Surgical Sciences and Biotechnology, Sapienza University of Rome, 00185 Rome, Italy
Martina Leopizzi
Department of Medico-Surgical Sciences and Biotechnology, Sapienza University of Rome, 00185 Rome, Italy
Carla Giordano
Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00185 Rome, Italy
Antonio Greco
Department of Sense Organs, Sapienza University of Rome, Viale del Policlinico 155, 00185 Rome, Italy
Paola Tirassa
Institute of Biochemistry and Cell Biology, National Research Council (IBBC-CNR), Department of Sense Organs, Sapienza University of Rome, Viale del Policlinico 155, 00185 Rome, Italy
Cinzia Severini
Institute of Biochemistry and Cell Biology, National Research Council (IBBC-CNR), Department of Sense Organs, Sapienza University of Rome, Viale del Policlinico 155, 00185 Rome, Italy
Massimo Fusconi
Department of Sense Organs, Sapienza University of Rome, Viale del Policlinico 155, 00185 Rome, Italy
Primary Sjögren’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.
