Abstract
BackgroundHeat shock protein (HSP) 20 is a molecular chaperone that exerts multiple protective functions in various kinds of tissues. However, the expression of HSP20 and its specific functions in airway epithelial cells (AECs) remain elusive.ResultsIn current study, we first confirmed the inducible expression of HSP20 in mouse AECs and in a human bronchial epithelial cell line BEAS-2B cells, under different oxidant stressors. Then by establishing a HSP20-abundant mouse model with repeated low-level-ozone exposures and stimulating this model with a single high-level ozone exposure, we found that the HSP20 abundance along with its enhanced phosphorylation potentially contributed to the alleviation of oxidative injuries, evidenced by the decreases in the bodyweight reduction, the BAL neutrophil accumulation, the AECs shedding, and the BAL concentrations of albumin and E-cadherin. The biological function of HSP20 and its molecular mechanisms were further investigated in BEAS-2B cells that were transfected with HSP20-, unphosphorylatable HSP20(Ala) or empty vector plasmids prior to the stimulation of H2O2, of which its oxidant capacity has been proved to be similar with those of ozone in an air–liquid culture system. We found that the H2O2-induced intracellular ROS level and the early cell apoptosis were attenuated in the HSP20- but not HSP20(Ala)- transfected cells. The intracellular expression of NQO-1 (mRNA and protein) and the intranuclear content of Nrf2 were significantly increased in the HSP20- transfected cells but not in the HSP20(Ala)- and empty vector-transfected cells after the stimulation of H2O2.ConclusionsThe inducible expression of HSP20 in AECs by oxidative stress exerts protective roles against oxidative damages, which may involve the activation of the Nrf2-NQO-1 pathway.
Highlights
Oxidative stress plays an important role in the pathogenesis of chronic inflammatory airway disease, including chronic asthma and chronic obstructive pulmonary disease (COPD) [1]
The stable abundant expression of HSP20 in airway epithelial cells (AECs) of mice preconditioned with repeated low‐level‐ozone exposures In the pilot experiment, IHC staining showed that HSP20 expression was induced in mouse AECs after different level of ozone exposures, even at a level as low as 0.5 ppm (Fig. 2a)
By using in vivo and in vitro models, we demonstrated that HSP20 can be induced by oxidative stresses in mouse and human AECs, which can in turn protect AECs from oxidative injuries through mechanisms that involve the NF-E2 related factor 2 (Nrf2)-NAD(P)H quinone oxidoreductase 1 (NQO-1) pathway
Summary
Oxidative stress plays an important role in the pathogenesis of chronic inflammatory airway disease, including chronic asthma and chronic obstructive pulmonary disease (COPD) [1]. As the first line of host defense, airway epithelial cells (AECs) as well as their intercellular adjacent junctions are vulnerable. Bao et al Cell Biosci (2020) 10:120 to oxidative injuries, as they are frequently exposed to enormous kinds of airborne oxidants, such as ozone [2, 3]. The survival of AECs under oxidant insults relies on the intracellular redox homeostasis, which is maintained by the balance between reactive oxygen species (ROS) and antioxidant enzymes [4]. Antioxidant enzymes like NAD(P)H quinone oxidoreductase 1 (NQO-1), and glutathione S-transferases (GST) are sensitive to exogeneous oxidants [6, 7]. The activity of this Nrf2-NQO-1 pathway is considered to be a vital component of antioxidant capacity in mammalian cells. The expression of HSP20 and its specific functions in airway epithelial cells (AECs) remain elusive
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