Heme oxygenase (HO), the
heme-degrading
enzyme, has shown anti-inflammatory effects in several models of
pulmonary diseases. HO is induced in airways during
asthma; however, its functional role is unclear. Therefore, we evaluated the role of HO on airway
inflammation [evaluated by bronchoalveolar lavage (BAL) cellularity and BAL levels of eotaxin,
PGE(2), and
proteins], mucus secretion (evaluated by analysis of MUC5AC gene expression and
periodic acid-Schiff staining), oxidative stress (evaluated by quantification of 4-hydroxynonenal adducts and carbonylated
protein levels in lung homogenates), and airway responsiveness to
histamine in
ovalbumin (OVA)-sensitized and multiple
aerosol OVA or saline-challenged guinea pigs (6 challenges, once daily, OVA group and control group, respectively). Airway
inflammation, mucus secretion, oxidative stress, and responsiveness were significantly increased in the OVA group compared with the control group. HO upregulation by repeated administrations of
hemin (50 mg/kg i.p.) significantly decreased airway responsiveness in control animals and airway
inflammation, mucus secretion, oxidative stress, and responsiveness in OVA animals. These effects were reversed by the concomitant administration of the HO inhibitor
tin protoporphyrin-IX (50 micromol/kg i.p.). Repeated administrations of
tin protoporphyrin-IX alone significantly increased airway responsiveness in control animals but did not modify airway
inflammation, mucus secretion, oxidative stress, and responsiveness in OVA animals. These results suggest that upregulation of the HO pathway has a significant protective effect against airway
inflammation, mucus hypersecretion, oxidative stress, and hyperresponsiveness in a model of allergic
asthma in guinea pigs.