P2Y2 nucleotide receptor activation up-regulates vascular cell adhesion molecular-1 expression and enhances lymphocyte adherence to a human submandibular gland cell line

Olga J. Baker, Jean M. Camden, Danny E. Rome, Cheikh I. Seye, Gary A. Weisman

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Sjögren's syndrome (SS) is a chronic inflammatory autoimmune disease that causes salivary and lacrimal gland tissue destruction resulting in impaired secretory function. Although lymphocytic infiltration of salivary epithelium is associated with SS, the mechanisms involved have not been adequately elucidated. Our previous studies have shown that the G protein-coupled P2Y2 nucleotide receptor (P2Y2R) is up-regulated in response to damage or stress of salivary gland epithelium, and in salivary glands of the NOD.B10 mouse model of SS-like autoimmune exocrinopathy. Additionally, we have shown that P2Y2R activation up-regulates vascular cell adhesion molecule-1 (VCAM-1) expression in endothelial cells leading to the binding of monocytes. The present study demonstrates that activation of the P2Y2R in dispersed cell aggregates from rat submandibular gland (SMG) and in human submandibular gland ductal cells (HSG) up-regulates the expression of VCAM-1. Furthermore, P2Y2R activation mediated the up-regulation of VCAM-1 expression in HSG cells leading to increased adherence of lymphocytic cells. Inhibitors of EGFR phosphorylation and metalloprotease activity abolished P2Y2R-mediated VCAM-1 expression and decreased lymphocyte binding to HSG cells. Moreover, silencing of EGFR expression abolished UTP-induced VCAM-1 up-regulation in HSG cells. These results suggest that P2Y2R activation in salivary gland cells increases the EGFR-dependent expression of VCAM-1 and the binding of lymphocytes, a pathway relevant to inflammation associated with SS.

Original languageEnglish (US)
Pages (from-to)65-75
Number of pages11
JournalMolecular Immunology
Volume45
Issue number1
DOIs
StatePublished - Jan 2008
Externally publishedYes

Keywords

  • EGF receptor
  • Inflammation
  • Metalloproteases
  • P2Y receptor
  • Sjögren's syndrome
  • VCAM-1

ASJC Scopus subject areas

  • Immunology
  • Molecular Biology

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