title: Chronic inflammation enhances NGF-β/TrkA system expression via EGFR/MEK/ERK pathway activation in Sjögren's syndrome.
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.
  
  
  CONCLUSIONS
  NGF-β and TrkA expression is elevated in salivary gland epithelial cells of primary Sjögren's syndrome (pSS). Overexpression of NGF-β/TrkA system in pSS occurs via EGFR/Raf-1/MEK/ERK pathway. In pSS, NGF-β overexpression was prevented by EGFR/Raf-1/MEK/ERK pathway inhibition.
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sense Organs, Section of Human Anatomy and Histology, Laboratory of Cell Biology, University of Bari Medical School, Bari, Italy, sabrina.lisi@uniba.it.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Lisi
authors.forename: Margherita
authors.initials: M
authors.lastname: Sisto
authors.forename: Domenico
authors.initials: D
authors.lastname: Ribatti
authors.forename: Massimo
authors.initials: M
authors.lastname: D'Amore
authors.forename: Raffella
authors.initials: R
authors.lastname: De Lucro
authors.forename: Maria Antonia
authors.initials: MA
authors.lastname: Frassanito
authors.forename: Loredana
authors.initials: L
authors.lastname: Lorusso
authors.forename: Angelo
authors.initials: A
authors.lastname: Vacca
authors.forename: Dario Domenico
authors.initials: DD
authors.lastname: Lofrumento
mesh_terms: D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D002908:Chronic Disease; D016207:Cytokines / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D066246:ErbB Receptors / Q000276:immunology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D020935:MAP Kinase Signaling System; D008297:Male; D008875:Middle Aged; D020932:Nerve Growth Factor / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D020917:Receptor, trkA / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D012469:Salivary Glands / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D012859:Sjogren's Syndrome / Q000150:complications / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D016207:Cytokines; D020932:Nerve Growth Factor; D066246:ErbB Receptors; D020917:Receptor, trkA