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 journalArticle

7 Citations (Scopus)

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

Fingerprint

MAP Kinase Signaling System
Receptor Protein-Tyrosine Kinases
Nerve Growth Factor
Inflammation
Salivary Glands
Minor Salivary Glands
Epithelial Cells
Interleukin-6
Proto-Oncogene Proteins c-raf
Sialadenitis
Mitogen-Activated Protein Kinase Kinases
Epidermal Growth Factor
Autoimmune Diseases
Cell Culture Techniques
Phosphorylation
Cytokines
Biopsy

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)

Cite this

Lisi, S., Sisto, M., Ribatti, D., D'Amore, M., De Lucro, R., Frassanito, M. A., ... Lofrumento, D. D. (2014). Chronic inflammation enhances NGF-β/TrkA system expression via EGFR/MEK/ERK pathway activation in Sjögren's syndrome. Journal of Molecular Medicine, 92(5), 523-537. https://doi.org/10.1007/s00109-014-1130-9

Chronic inflammation enhances NGF-β/TrkA system expression via EGFR/MEK/ERK pathway activation in Sjögren's syndrome. / Lisi, Sabrina; Sisto, Margherita; Ribatti, Domenico; D'Amore, Massimo; De Lucro, Raffella; Frassanito, Maria Antonia; Lorusso, Loredana; Vacca, Angelo; Lofrumento, Dario Domenico.

In: Journal of Molecular Medicine, Vol. 92, No. 5, 2014, p. 523-537.

Research output: Contribution to journalArticle

Lisi, S, Sisto, M, Ribatti, D, D'Amore, M, De Lucro, R, Frassanito, MA, Lorusso, L, Vacca, A & Lofrumento, DD 2014, 'Chronic inflammation enhances NGF-β/TrkA system expression via EGFR/MEK/ERK pathway activation in Sjögren's syndrome', Journal of Molecular Medicine, vol. 92, no. 5, pp. 523-537. https://doi.org/10.1007/s00109-014-1130-9
Lisi, Sabrina ; Sisto, Margherita ; Ribatti, Domenico ; D'Amore, Massimo ; De Lucro, Raffella ; Frassanito, Maria Antonia ; Lorusso, Loredana ; Vacca, Angelo ; Lofrumento, Dario Domenico. / Chronic inflammation enhances NGF-β/TrkA system expression via EGFR/MEK/ERK pathway activation in Sjögren's syndrome. In: Journal of Molecular Medicine. 2014 ; Vol. 92, No. 5. pp. 523-537.
@article{ccaefaae5cff400ea97748497b7f0f37,
title = "Chronic inflammation enhances NGF-β/TrkA system expression via EGFR/MEK/ERK pathway activation in Sj{\"o}gren's syndrome",
abstract = "Primary Sj{\"o}gren'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.",
keywords = "EGFR, ERK, IL-6, MEK, NGF-β, Raf-1, Sj{\"o}gren's syndrome, TNF-α, TrkA",
author = "Sabrina Lisi and Margherita Sisto and Domenico Ribatti and Massimo D'Amore and {De Lucro}, Raffella and Frassanito, {Maria Antonia} and Loredana Lorusso and Angelo Vacca and Lofrumento, {Dario Domenico}",
year = "2014",
doi = "10.1007/s00109-014-1130-9",
language = "English",
volume = "92",
pages = "523--537",
journal = "Journal of Molecular Medicine",
issn = "0946-2716",
publisher = "Springer Verlag",
number = "5",

}

TY - JOUR

T1 - Chronic inflammation enhances NGF-β/TrkA system expression via EGFR/MEK/ERK pathway activation in Sjögren's syndrome

AU - Lisi, Sabrina

AU - Sisto, Margherita

AU - Ribatti, Domenico

AU - D'Amore, Massimo

AU - De Lucro, Raffella

AU - Frassanito, Maria Antonia

AU - Lorusso, Loredana

AU - Vacca, Angelo

AU - Lofrumento, Dario Domenico

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - EGFR

KW - ERK

KW - IL-6

KW - MEK

KW - NGF-β

KW - Raf-1

KW - Sjögren's syndrome

KW - TNF-α

KW - TrkA

UR - http://www.scopus.com/inward/record.url?scp=84899926766&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84899926766&partnerID=8YFLogxK

U2 - 10.1007/s00109-014-1130-9

DO - 10.1007/s00109-014-1130-9

M3 - Article

C2 - 24557415

AN - SCOPUS:84899926766

VL - 92

SP - 523

EP - 537

JO - Journal of Molecular Medicine

JF - Journal of Molecular Medicine

SN - 0946-2716

IS - 5

ER -