A 3D “In Vitro” Model to Study Hyaluronan Effect in Nasal Epithelial Cell Line Exposed to Double-Stranded RNA Poly(I:C)
Giusy Daniela Albano1, Anna Bonanno1, Daniela Giacomazza2, Luca Cavalieri3, Martina Sammarco3, Eleonora Ingrassia3, Rosalia Gagliardo1, Loredana Riccobono1, Monica Moscato1, Giulia Anzalone1, Angela Marina Montalbano1 and Mirella Profita1,*
1Institute for Biomedical Research and Innovation (IRIB), National Research Council of Italy (CNR), Palermo 90146,
2Institute of Biophysic, CNR, Palermo 90146,
3Chiesi Farmaceutici SpA, Parma 43122, Italy
E-mail: profita@irib.cnr.it
Tel: +39-091-6809121, Fax: +39-091-6809122
Received: July 23, 2019; Revised: September 3, 2019; Accepted: September 16, 2019; Published online: December 3, 2019.
© The Korean Society of Applied Pharmacology. All rights reserved.

Abstract
Environmental agents, including viral and bacterial infectious agents, are involved in the alteration of physicochemical and biological parameters in the nasal epithelium. Hyaluronan (HA) has an important role in the regulation of tissue healing properties. High molecular weight HA (HMW-HA) shows greater anti-inflammatory responses than medium molecular weight HA (MMW-HA) and low molecular weight HA (LMW-HA). We investigated the effect of HMW-HA, MMW-HA and LMW-HA on the regulation of physicochemical and biological parameters in an “in vitro” model that might mimic viral infections of the nasal epithelium. Human nasal epithelial cell line RPMI2650 was stimulated with double-stranded RNA (dsRNA) Poly(I:C) for 5 days in air-liquid-interface (ALI) culture (3D model of airway tissue). dsRNA Poly(I:C) treatment significantly decreased transepithelial electrical resistance (TEER) in the stratified nasal epithelium of RPMI2650 and increased pH values, rheological parameters (elastic G’ and viscous G’’), and Muc5AC and Muc5B production in the apical wash of ALI culture of RPMI2650 in comparison to untreated cells. RPMI2650 treated with dsRNA Poly(I:C) in the presence of HMW-HA showed lower pH values, Muc5AC and Muc5B production, and rheological parameters, as well as increased TEER values in ALI culture, compared to cells treated with Poly(I:C) alone or pretreated with LMW-HA and MMW-HA. Our 3D “in vitro” model of epithelium suggests that HMW-HA might be a coadjuvant in the pharmacological treatment of viral infections, allowing for the control of some physicochemical and biological properties affecting the epithelial barrier of the nose during infection.
Keywords: Hyaluronan, (dsRNA) Poly(I:C), Anti-inflammatory responses, Rheological properties, Mucins, Epithelial integrity


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