Table 1.
Sputum and BAL participant details.
FEV1: Forced expiratory volume in one second; FVC: forced vital capacity.
Table 2.
FEV1: Forced expiratory volume in one second; FVC: forced vital capacity.
Table 3.
List of forward and reverse primers and PCR conditions.
Fig 1.
MIF and HIF-1α expression levels in COPD.
MIF protein was measured in sputum (A; RV cohort), serum (B) and isolated BAL macrophages (C; RV cohort). HIF-1α protein concentration was measured in isolated BAL macrophages (D; RV Cohort). Data are expressed as mean±SEM. *p<0.05 and ***p<0.001 compared to non-smoking groups. Rhinovirus Infection (RV).
Fig 2.
MIF and HIf-1α correlations in COPD and HIF-1 α regulation of Mif expression.
Correlation analysis between HIF-1α and MIF protein concentrations in isolated BAL macrophages from non-smokers (A), smokers (B), and COPD patients (C). Chromatin immunoprecipitation analysis of HIF-1α binding to HRE1 and HRE2 sites in the Mif promoter in mouse lung tissue (D). Data are expressed as mean±SD for 6 animals per group. **p<0.01 compared to air controls.
Table 4.
Relative Mif mRNA expression in lungs of mouse models of COPD.
Äct values of Mif expression in lung tissue relative to Hprt (cigarette model) and 18s (ozone model) expression as measured by RT-qPCR. ND: not done.
Fig 3.
Effect of ISO-1 and dexamethasone on ozone-induced airway inflammatory cells.
Total cell count (A), neutrophil (B), macrophage (C), and lymphocyte (D) counts in mouse BAL samples. Data are expressed as mean±SD for 6 animals per group. *p<0.05 and **p<0.01 compared to air controls, # p<0.05 compared to ozone exposed group.
Fig 4.
Effect of ISO-1 and dexamethasone on ozone-induced BAL inflammation.
Cytokine protein levels in mouse BAL of ozone exposed and ISO-1- or dexamethasone-treated mice measured by ELISA. KC (A), GM-CSF (B), TNF-α (C) and MIF (D). Data are expressed as mean±SD for 6 animals per group. *p<0.05 and **p<0.01 compared to air controls, # p<0.05 compared to ozone exposed group.
Fig 5.
Effect of ISO-1 and dexamethasone on ozone-induced lung inflammation.
Cytokine mRNA (A, C, E & G) and protein (B, D, F & H) expression levels in the lung of ozone exposed and ISO-1- or dexamethasone-treated mice. KC (A&B), GM-CSF (C&D), TNF-α (E&F), and MIF (G&H). Data are expressed as mean±SD for 6 animals per group. *p<0.05 and **p<0.01 compared to air controls, #p<0.05 compared to ozone exposed group.
Fig 6.
Effect of ISO-1 and dexamethasone on ozone-induced changes in AHR and lung function.
Mouse lung function measurements of pulmonary resistance (RL; A), -logPC100 (B), FEV75 (C), lung compliance (Cchord; D), total lung capacity (TLC; E) and functional residual capacity (FRC; F). Data are expressed as mean±SD for 6 animals per group. *p<0.05 and **p<0.01 compared to air controls, #p<0.05 compared to ozone-exposed group.
Fig 7.
Effect of ISO-1 and dexamethasone in combination on ozone-induced lung inflammation.
Cytokine mRNA (A & C) and protein (B & D) expression levels in the lung of ozone exposed and the combination of ISO-1- plus dexamethasone-treated mice. KC (A&B) and MIF (C&D). Pulmonary resistance (RL; E) was also measured. Data are expressed as mean±SD for 6 animals per group. *p<0.05 and **p<0.01 compared to air controls, #p<0.05 compared to ozone exposed group.