Hyaluronidase expression and activity is regulated by pro-inflammatory cytokines in human airway epithelial cells

María Elena Monzón, Dahis Manzanares, Nathalie Schmid, S. Marina Casalino-Matsuda, Rosanna M. Forteza

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


Hyaluronan (HA) is present at the apical surface of airway epithelium as a high-molecular-weight polymer. Since HA depolymerization initiates a cascade of events that results in kinin generation and growth factor processing, in the present work we used primary cultures of human bronchial epithelial (HBE) cells grown at the air-liquid interface (ALI) to assess hyaluronidase (Hyal) activity by HA zymography, gene expression by quantitative real-time PCR, and localization by confocal microscopy. Because TNF-α and IL-1β induce Hyals in other cells, we tested their effects on Hyals expression and activity. We found that Hyal-like activity is present in the apical and basolateral secretions from HBE cells where Hyals 1, 2, and 3 are expressed, and that IL-1β acts synergistically with TNF-α to increase gene expression and activity. Confocal microscopy showed that Hyals 1, 2, and 3 were localized intracellularly, while Hyal2 was also expressed at the apical pole associated with the plasma membrane, and in a soluble form on the apical secretions. Tissue sections from normal individuals and from individuals with asthma showed a Hyal distribution pattern similar to that observed on nontreated HBE cells or exposed to cytokines, respectively. In addition, increased expression and activity were observed in tracheal sections and in bronchoalveolar lavage (BAL) obtained from subjects with asthma when compared with normal lung donors and healthy volunteers. Our observations indicate that Hyal 1, 2, and 3 are expressed in airway epithelium and may operate in a coordinated fashion to depolymerize HA during inflammation associated with up-regulation of TNF-α and IL-1β, such as allergen-induced asthmatic responses.

Original languageEnglish (US)
Pages (from-to)289-295
Number of pages7
JournalAmerican journal of respiratory cell and molecular biology
Issue number3
StatePublished - Sep 1 2008


  • Airway
  • Asthma
  • Hyaluronan
  • Hyaluronidase
  • Inflammation

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology


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