Increased Siglec-1 Expression in Monocytes of Patients with Primary Biliary Cirrhosis

Abstract

Objectives: To evaluate Siglec-1 protein (CD169) and mRNA levels in peripheral blood monocytes of patients with primary biliary cirrhosis (PBC) and investigate its role in PBC pathogenesis by looking for correlations between Siglec-1 expression and key PBC associated biochemical indices. Methods: FACS analysis was used to identify the percentage of peripheral blood monocytes positive for both CD14 and Siglec-1 in (a) 45 PBC patients, (b) 40 patients with liver cirrhosis after hepatitis B infection and (c) 36 healthy controls. Siglec-1 mRNA was measured by real-time RT-PCR and serum biomarkers by routine biochemistry. Results: The percentage of CD14-Siglec-1 double positive cells was significantly higher (p< 0.01) in PBC patients than in healthy controls or cirrhosis post-hepatitis patients (13.68 ± 2.44%, 1.0 ± 0.2 %, and 4.1 ± 0.5 %, respectively). Siglec-1 mRNA expression in the PBC group was 3.42 times higher than in healthy controls (p < 0.01). Conclusion: We investigated the role of Siglec-1 in PBC by assessing its expression in mononuclear cells of PBC patients and levels of secreted cytokines in cell supernatants after Siglec-1 RNA interference. It is possible that elevated Siglec-1 expression in peripheral blood monocytes of PBC patients is correlated with monocyte-mediated inflammatory responses during the development of PBC.

Keywords:

• Primary biliary cirrhosis
• Siglec-1
• Expression
• Biomarkers
• Inflammatory responses

ACKNOWLEDGMENTS

This research was supported by grants from the Ministry of Science and Technology (2006AA02Z496), National Science Foundation of China (30671840, 30772017, 30770997, 30972730), Shanghai Municipal Commission for Science and Technology (09JC1405400, 08QH14001, 07XD14013).