CD40-CD40 ligand signal induces the intercellular adhesion molecule-1 expression through nuclear factor-kappa B p50 in cultured salivary gland epithelial cells from patients with Sjögren's syndrome

• DOI: 10.1007/s10165-006-0538-7
• Publication Date: 2007-02-03T06:55:52Z
• Authors: Miwako Saito; Yasuhiro Ota; Hiroyuki Ohashi; Yoshiaki Dei; Kumiko Shimoyama; Daisuke Suzuki; Hideharu Hayashi; Noriyoshi Ogawa
• Keywords: Adult; Male; 0301 basic medicine; CD40 Ligand; NF-kappa B p50 Subunit; Middle Aged; Intercellular Adhesion Molecule-1; Salivary Glands; Up-Regulation; 03 medical and health sciences; Sjogren's Syndrome; Humans; Female; CD40 Antigens; Cells, Cultured; Aged; Signal Transduction

The purpose of this study is to clarify signal transduction of expression of the intercellular adhesion molecule-1 (ICAM-1) via CD40-CD40 ligand in salivary glands of patients with Sjögren's syndrome (SS). We used cultured salivary gland epithelial cells (SG cells) from 15 SS patients and 8 controls obtained by labial minor salivary gland biopsy. First, ICAM-1 expression was determined with reverse transcriptase-polymerase chain reaction and flow cytometry in the presence or absence of soluble CD40L (sCD40L). Next, SG cells were transfected with plasmids of pGL1.3-Luc inserted with promoter region of ICAM-1, pGL1.3kB(-)-Luc mutated in nuclear factor kappa-B (NF-kappaB) binding site of pGL1.3-Luc and pNF-kappaB-Luc by lipofection method. Luciferase activity of the cells was measured in the presence or absence of sCD40L or sCD40L and an NF-kappaB inhibitor, pyrrolidine dithiocarbamate (PDTC). Finally NF-kappaB family proteins of cell nuclear extracts were determined. ICAM-1 expression was significantly enhanced with sCD40L at the mRNA and protein level. Activity of pNF-kappaB-Luc and pGL1.3-Luc was significantly elevated by stimulation with sCD40L and suppressed by PDTC. NF-kappaB p50 protein level was elevated by stimulation with sCD40L and suppressed by PDTC. Our results suggest that sCD40L enhances the ICAM-1 expression by activation of NF-kappaB p50 in the SS SG cells.