Exposure to
ozone has been associated with airway
inflammation and
glucocorticoid insensitivity. This study aimed to observe the capacity of anti-murine
interleukin-17A monoclonal antibody (IL-17mAb) to reverse
ozone-induced
glucocorticoid insensitivity and to detect its effects with
glucocorticoids in protecting against airway
inflammation. After C57/BL6 mice were exposed to
ozone (2.5 ppm; 3 h) for 12 times over 6 weeks, PBS, IL-17mAb (50 ug/ml),
dexamethasone (2 mg/kg), and combination administration of IL-17mAb (50 ug/ml) and
dexamethasone (2 mg/kg) were intraperitoneally injected into mice at a dose of 0.1 ml, respectively, for 10 times over 5 weeks. At sacrifice, lung histology, airway inflammatory cells, levels of related
cytokines in bronchoalveolar lavage fluid (BALF), and serum were analyzed, airway inflammatory cell infiltration density and mean linear intercept (Lm) were measured, the expression of
IL-17A mRNA,
glucocorticoid receptors (GR), NF-κB, and
p38 mitogen-activated protein kinase (MAPK) phosphorylation were determined. We found that combination administration markedly reduced
ozone-induced total inflammatory cells, especially neutrophils; inhibited levels of
cytokines, including
IL-8,
IL-17A, and TNF-α in BALF; and suppressed airway inflammatory cell infiltration density and Lm. Additionally, combination administration significantly elevated levels of IFN-γ in BALF, decreased the
dexamethasone-induced increase of
IL-17A mRNA, and increased the expression of GR and decrement of NF-κB and p38MAPK phosphorylation, which are also related to
glucocorticoids insensitivity. Collectively, combination administration shows profound efficacy in inhibiting certain
cytokines, and
IL-17 mAb partly improved the
glucocorticoids insensitivity via modulating the enhanced production rate and improving expression of
IL-17A induced by
glucocorticoids administration and p38MAPK, NF-κB signaling pathway.