Chronic inflammation enhances NGF-β/TrkA system expression via EGFR/MEK/ERK pathway activation in Sjögren's syndrome

Sabrina Lisi, Margherita Sisto, Domenico Ribatti, Massimo D'Amore, Raffella De Lucro, Maria Antonia Frassanito, Loredana Lorusso, Angelo Vacca, Dario Domenico Lofrumento

Research output: Contribution to journalArticlepeer-review

Abstract

Primary Sjögren's syndrome (pSS) is a chronic autoimmune exocrine disease associated with variable lymphocytic infiltration of the affected organs (primarily salivary and lachrymal glands). To investigate the potential implication of nerve growth factor-β (NGF-β) and its high affinity receptor tyrosine kinase receptor A (TrkA) in the regulation of pSS inflammatory responses, we studied their expression in the human salivary gland epithelial cells (SGEC) cultures from pSS minor salivary glands (MSG) biopsies and their relationship with histopathological disease parameters. Here, we demonstrated an increased expression of the NGF-β/TrkA system in pSS SGEC, correlated with the MSG inflammation grade. The results demonstrate that the pro-inflammatory cytokines TNF-α and IL-6 enhance NGF-β production; on the contrary, NGF-β production was reduced in the presence of both Raf-1 kinase and MEK inhibitors. Furthermore, TNF-α/IL-6 treatment increased ERK1/2 phosphorylation. Inhibition of the EGF/EGFR system also decreased NGF-β release by pSS SGEC, indicating that the chronic inflammatory condition characteristic of pSS enhances NGF-β production via EGFR/Raf-1/MEK/ERK pathway activation.

Original languageEnglish
Pages (from-to)523-537
Number of pages15
JournalJournal of Molecular Medicine
Volume92
Issue number5
DOIs
Publication statusPublished - 2014

Keywords

  • EGFR
  • ERK
  • IL-6
  • MEK
  • NGF-β
  • Raf-1
  • Sjögren's syndrome
  • TNF-α
  • TrkA

ASJC Scopus subject areas

  • Drug Discovery
  • Genetics(clinical)
  • Molecular Medicine
  • Medicine(all)

Fingerprint Dive into the research topics of 'Chronic inflammation enhances NGF-β/TrkA system expression via EGFR/MEK/ERK pathway activation in Sjögren's syndrome'. Together they form a unique fingerprint.

Cite this