Potential Involvement of the Epidermal Growth Factor Receptor Ligand Epiregulin and Matrix Metalloproteinase-1 in Pathogenesis of Chronic Rhinosinusitis.

Potential Involvement of the Epidermal Growth Factor Receptor Ligand Epiregulin and Matrix Metalloproteinase-1 in Pathogenesis of Chronic Rhinosinusitis.

Am J Respir Cell Mol Biol. 2017 Apr 11;:

Authors: Homma T, Kato A, Sakashita M, Takabayashi T, Norton JE, Suh LA, Carter RG, Harris KE, Peters AT, Grammer LC, Min JY, Shintani-Smith S, Tan BK, Welch K, Conley DB, Kern RC, Schleimer RP

Abstract
RATIONALE: Chronic rhinosinusitis (CRS) is a heterogeneous chronic inflammatory disease of the nose and paranasal sinuses that presents without (CRSsNP) or with nasal polyps (CRSwNP). Features of CRSwNP are the frequent presence of type 2 allergic inflammation and high prevalence of Staphylococcus aureus (SA) colonization. As inflammation persists, sinus tissue undergoes epithelial damage and repair along with polyp growth. Since one feature of damaged tissue is enhancement of growth factor signaling, we evaluated the presence of EGFR ligands and MMPs in CRS. The objective of this study was to analyze the expression of EGFR ligands and MMPs in patients with CRS and investigate the possible role of SA on epithelial activation.
METHODS AND RESULTS: Sinonasal tissues were collected during surgery from control subjects and patients with CRS. Tissues were processed as described previously for analysis of mRNA (RT-PCR) and proteins (ELISA) for the majority of EGFR ligands within the tissue extracts. Elevated expression of EREG and MMP-1 mRNA and protein was observed in uncinate and polyp tissue from patients with CRSwNP. IHC study of clinical samples revealed that airway epithelial cells expressed both of these proteins. Cultured primary human airway epithelial cells expressed MMP-1, and MMP-1 was further induced by stimulation with EREG or heat-killed SA (HKSA). The induction of MMP-1 by HKSA was blocked by an antibody against EREG.
CONCLUSIONS: Elevated expression of EREG and MMP-1 may be related to polyp formation in CRS and colonization of SA might further enhance this process.

PMID: 28398769 [PubMed - as supplied by publisher]

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