Nebulized Hyaluronan Ameliorates lung inflammation in cystic fibrosis mice

Manuela Gavina, Alessandro Luciani, Valeria R. Villella, Speranza Esposito, Eleonora Ferrari, Ilaria Bressani, Alida Casale, Emanuela M. Bruscia, Luigi Maiuri, Valeria Raia

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Rationale Chronic lung inflammation with increased susceptibility to bacterial infections cause much of the morbidity and mortality in patients with cystic fibrosis (CF), the most common severe, autosomal recessively inherited disease in the Caucasian population. Exogenous inhaled hyaluronan (HA) can exert a protective effect against injury and beneficial effects of HA have been shown in experimental models of chronic respiratory diseases. Our objective was to examine whether exogenous administration of nebulized HA might interfere with lung inflammation in CF. Study design/methods F508del homozygous mice (Cftr F508del) and transgenic mice overexpressing the ENaC channel β-subunit (Scnn1b-Tg) were treated with nebulized HA (0.5 mg/mouse/day for 7 days). Tumor necrosis factor-alpha (TNFα), macrophage inflammatory protein-2 (MIP-2), myeloperoxidase (MPO) levels, and macrophage infiltration were assessed on lung tissues. IB3-1 and CFBE41o-epithelial cell lines were cultured with HA (24 hr, 100 μg/ml) and Reactive Oxygen Species (ROS), Tissue Transglutaminase (TG2) SUMOylation and Peroxisome Proliferator Activated Receptor gamma (PPARγ) and phospho-p42/p44 levels were measured by dichlorodihydrofluorescein assay, or fluorescence resonance energy transfer (FRET) microscopy or immunoblots. Results Nebulized HA reduced TNFα expression (P <0.005); TNFα, MIP-2, and MPO protein levels (P <0.05); MPO activity (P <0.05); and CD68+ cells counts (P <0.005) in lung tissues of CftrF508del and Scnn1b-Tg mice, compared with saline-treated mice. HA reduced ROS, TG2 SUMOylation, TG2 activity, phospho-p42-44, and increased PPARγ protein in both IB3-1 and CFBE41o cells (P <0.05). Conclusions Nebulized HA is effective in controlling inflammation in vivo in mice CF airways and in vitro in human airway epithelial cells. We provide the proof of concept for the use of inhaled HA as a potential anti-inflammatory drug in CF therapy.

Original languageEnglish
Pages (from-to)761-771
Number of pages11
JournalPediatric Pulmonology
Volume48
Issue number8
DOIs
Publication statusPublished - 2013

Fingerprint

Hyaluronic Acid
Cystic Fibrosis
Pneumonia
Chemokine CXCL2
Sumoylation
Peroxidase
Tumor Necrosis Factor-alpha
PPAR gamma
Reactive Oxygen Species
Epithelial Cells
Lung
Fluorescence Resonance Energy Transfer
Bacterial Infections
Transgenic Mice
Microscopy
Proteins
Chronic Disease
Anti-Inflammatory Agents
Theoretical Models
Cell Count

Keywords

  • cystic fibrosis
  • Hyaluronan
  • inflammation

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Pulmonary and Respiratory Medicine

Cite this

Gavina, M., Luciani, A., Villella, V. R., Esposito, S., Ferrari, E., Bressani, I., ... Raia, V. (2013). Nebulized Hyaluronan Ameliorates lung inflammation in cystic fibrosis mice. Pediatric Pulmonology, 48(8), 761-771. https://doi.org/10.1002/ppul.22637

Nebulized Hyaluronan Ameliorates lung inflammation in cystic fibrosis mice. / Gavina, Manuela; Luciani, Alessandro; Villella, Valeria R.; Esposito, Speranza; Ferrari, Eleonora; Bressani, Ilaria; Casale, Alida; Bruscia, Emanuela M.; Maiuri, Luigi; Raia, Valeria.

In: Pediatric Pulmonology, Vol. 48, No. 8, 2013, p. 761-771.

Research output: Contribution to journalArticle

Gavina, M, Luciani, A, Villella, VR, Esposito, S, Ferrari, E, Bressani, I, Casale, A, Bruscia, EM, Maiuri, L & Raia, V 2013, 'Nebulized Hyaluronan Ameliorates lung inflammation in cystic fibrosis mice', Pediatric Pulmonology, vol. 48, no. 8, pp. 761-771. https://doi.org/10.1002/ppul.22637
Gavina M, Luciani A, Villella VR, Esposito S, Ferrari E, Bressani I et al. Nebulized Hyaluronan Ameliorates lung inflammation in cystic fibrosis mice. Pediatric Pulmonology. 2013;48(8):761-771. https://doi.org/10.1002/ppul.22637
Gavina, Manuela ; Luciani, Alessandro ; Villella, Valeria R. ; Esposito, Speranza ; Ferrari, Eleonora ; Bressani, Ilaria ; Casale, Alida ; Bruscia, Emanuela M. ; Maiuri, Luigi ; Raia, Valeria. / Nebulized Hyaluronan Ameliorates lung inflammation in cystic fibrosis mice. In: Pediatric Pulmonology. 2013 ; Vol. 48, No. 8. pp. 761-771.
@article{7b8c97e5758547ea941fdf01aa84988c,
title = "Nebulized Hyaluronan Ameliorates lung inflammation in cystic fibrosis mice",
abstract = "Rationale Chronic lung inflammation with increased susceptibility to bacterial infections cause much of the morbidity and mortality in patients with cystic fibrosis (CF), the most common severe, autosomal recessively inherited disease in the Caucasian population. Exogenous inhaled hyaluronan (HA) can exert a protective effect against injury and beneficial effects of HA have been shown in experimental models of chronic respiratory diseases. Our objective was to examine whether exogenous administration of nebulized HA might interfere with lung inflammation in CF. Study design/methods F508del homozygous mice (Cftr F508del) and transgenic mice overexpressing the ENaC channel β-subunit (Scnn1b-Tg) were treated with nebulized HA (0.5 mg/mouse/day for 7 days). Tumor necrosis factor-alpha (TNFα), macrophage inflammatory protein-2 (MIP-2), myeloperoxidase (MPO) levels, and macrophage infiltration were assessed on lung tissues. IB3-1 and CFBE41o-epithelial cell lines were cultured with HA (24 hr, 100 μg/ml) and Reactive Oxygen Species (ROS), Tissue Transglutaminase (TG2) SUMOylation and Peroxisome Proliferator Activated Receptor gamma (PPARγ) and phospho-p42/p44 levels were measured by dichlorodihydrofluorescein assay, or fluorescence resonance energy transfer (FRET) microscopy or immunoblots. Results Nebulized HA reduced TNFα expression (P <0.005); TNFα, MIP-2, and MPO protein levels (P <0.05); MPO activity (P <0.05); and CD68+ cells counts (P <0.005) in lung tissues of CftrF508del and Scnn1b-Tg mice, compared with saline-treated mice. HA reduced ROS, TG2 SUMOylation, TG2 activity, phospho-p42-44, and increased PPARγ protein in both IB3-1 and CFBE41o cells (P <0.05). Conclusions Nebulized HA is effective in controlling inflammation in vivo in mice CF airways and in vitro in human airway epithelial cells. We provide the proof of concept for the use of inhaled HA as a potential anti-inflammatory drug in CF therapy.",
keywords = "cystic fibrosis, Hyaluronan, inflammation",
author = "Manuela Gavina and Alessandro Luciani and Villella, {Valeria R.} and Speranza Esposito and Eleonora Ferrari and Ilaria Bressani and Alida Casale and Bruscia, {Emanuela M.} and Luigi Maiuri and Valeria Raia",
year = "2013",
doi = "10.1002/ppul.22637",
language = "English",
volume = "48",
pages = "761--771",
journal = "Pediatric Pulmonology",
issn = "8755-6863",
publisher = "Wiley-Liss Inc.",
number = "8",

}

TY - JOUR

T1 - Nebulized Hyaluronan Ameliorates lung inflammation in cystic fibrosis mice

AU - Gavina, Manuela

AU - Luciani, Alessandro

AU - Villella, Valeria R.

AU - Esposito, Speranza

AU - Ferrari, Eleonora

AU - Bressani, Ilaria

AU - Casale, Alida

AU - Bruscia, Emanuela M.

AU - Maiuri, Luigi

AU - Raia, Valeria

PY - 2013

Y1 - 2013

N2 - Rationale Chronic lung inflammation with increased susceptibility to bacterial infections cause much of the morbidity and mortality in patients with cystic fibrosis (CF), the most common severe, autosomal recessively inherited disease in the Caucasian population. Exogenous inhaled hyaluronan (HA) can exert a protective effect against injury and beneficial effects of HA have been shown in experimental models of chronic respiratory diseases. Our objective was to examine whether exogenous administration of nebulized HA might interfere with lung inflammation in CF. Study design/methods F508del homozygous mice (Cftr F508del) and transgenic mice overexpressing the ENaC channel β-subunit (Scnn1b-Tg) were treated with nebulized HA (0.5 mg/mouse/day for 7 days). Tumor necrosis factor-alpha (TNFα), macrophage inflammatory protein-2 (MIP-2), myeloperoxidase (MPO) levels, and macrophage infiltration were assessed on lung tissues. IB3-1 and CFBE41o-epithelial cell lines were cultured with HA (24 hr, 100 μg/ml) and Reactive Oxygen Species (ROS), Tissue Transglutaminase (TG2) SUMOylation and Peroxisome Proliferator Activated Receptor gamma (PPARγ) and phospho-p42/p44 levels were measured by dichlorodihydrofluorescein assay, or fluorescence resonance energy transfer (FRET) microscopy or immunoblots. Results Nebulized HA reduced TNFα expression (P <0.005); TNFα, MIP-2, and MPO protein levels (P <0.05); MPO activity (P <0.05); and CD68+ cells counts (P <0.005) in lung tissues of CftrF508del and Scnn1b-Tg mice, compared with saline-treated mice. HA reduced ROS, TG2 SUMOylation, TG2 activity, phospho-p42-44, and increased PPARγ protein in both IB3-1 and CFBE41o cells (P <0.05). Conclusions Nebulized HA is effective in controlling inflammation in vivo in mice CF airways and in vitro in human airway epithelial cells. We provide the proof of concept for the use of inhaled HA as a potential anti-inflammatory drug in CF therapy.

AB - Rationale Chronic lung inflammation with increased susceptibility to bacterial infections cause much of the morbidity and mortality in patients with cystic fibrosis (CF), the most common severe, autosomal recessively inherited disease in the Caucasian population. Exogenous inhaled hyaluronan (HA) can exert a protective effect against injury and beneficial effects of HA have been shown in experimental models of chronic respiratory diseases. Our objective was to examine whether exogenous administration of nebulized HA might interfere with lung inflammation in CF. Study design/methods F508del homozygous mice (Cftr F508del) and transgenic mice overexpressing the ENaC channel β-subunit (Scnn1b-Tg) were treated with nebulized HA (0.5 mg/mouse/day for 7 days). Tumor necrosis factor-alpha (TNFα), macrophage inflammatory protein-2 (MIP-2), myeloperoxidase (MPO) levels, and macrophage infiltration were assessed on lung tissues. IB3-1 and CFBE41o-epithelial cell lines were cultured with HA (24 hr, 100 μg/ml) and Reactive Oxygen Species (ROS), Tissue Transglutaminase (TG2) SUMOylation and Peroxisome Proliferator Activated Receptor gamma (PPARγ) and phospho-p42/p44 levels were measured by dichlorodihydrofluorescein assay, or fluorescence resonance energy transfer (FRET) microscopy or immunoblots. Results Nebulized HA reduced TNFα expression (P <0.005); TNFα, MIP-2, and MPO protein levels (P <0.05); MPO activity (P <0.05); and CD68+ cells counts (P <0.005) in lung tissues of CftrF508del and Scnn1b-Tg mice, compared with saline-treated mice. HA reduced ROS, TG2 SUMOylation, TG2 activity, phospho-p42-44, and increased PPARγ protein in both IB3-1 and CFBE41o cells (P <0.05). Conclusions Nebulized HA is effective in controlling inflammation in vivo in mice CF airways and in vitro in human airway epithelial cells. We provide the proof of concept for the use of inhaled HA as a potential anti-inflammatory drug in CF therapy.

KW - cystic fibrosis

KW - Hyaluronan

KW - inflammation

UR - http://www.scopus.com/inward/record.url?scp=84881385110&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84881385110&partnerID=8YFLogxK

U2 - 10.1002/ppul.22637

DO - 10.1002/ppul.22637

M3 - Article

C2 - 22825912

AN - SCOPUS:84881385110

VL - 48

SP - 761

EP - 771

JO - Pediatric Pulmonology

JF - Pediatric Pulmonology

SN - 8755-6863

IS - 8

ER -