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. Author manuscript; available in PMC: 2020 May 19.
Published in final edited form as: Sci Transl Med. 2019 Aug 28;11(507):eaav3879. doi: 10.1126/scitranslmed.aav3879

Figure 3. Cathelicidin responses to bacterial infection are impaired by inhaled corticosteroid and negatively correlate with COPD exacerbation severity.

Figure 3

(A) Stable state sputum hCAP18/LL-37 concentrations were measured in 37 subjects with COPD (GOLD stage 0-II) and 19 healthy control subjects by ELISA. (B) Cathelicidin-related anti-microbial peptide (CRAMP) concentrations were measured in mice at 10 days following intranasal treatment with 1.2 units of porcine pancreatic elastase or PBS control. (C) Correlation between sputum hCAP18/LL-37 and Streptococcal qPCR copies in 23 subjects with COPD. (D) C57BL/6 mice were treated intranasally with fluticasone propionate (20μg) or vehicle DMSO control and challenged intranasally with S. pneumoniae D39. CRAMP concentrations in BAL were measured by ELISA at the indicated timepoints. (E) C57BL/6 mice were treated intranasally with porcine pancreatic elastase or PBS control. Ten days later, mice were treated intranasally with fluticasone propionate, challenged with S.pneumoniae D39 and CRAMP concentrations in BAL measured at 8 hours post-infection. (F) Subjects with COPD (n=27) were monitored prospectively and sputum samples taken during exacerbation. Sputum hCAP18/LL-37 concentrations were measured by ELISA at the indicated timepoints. (G) Correlation between sputum hCAP18/LL-37 and FEV1 decline, sputum MUC5AC concentrations and sputum bacterial loads. (H, left) BEAS-2B cells were treated with 1 or 10nM fluticasone propionate, stimulated with S. pneumoniae D39 and hCAP18/LL-37 concentrations in cell supernatants were measured at 8 hours by ELISA. (h, right) Primary bronchial epithelial cells from 6 subjects with COPD were cultured, treated with 10nM FP, stimulated ex vivo with S. pneumoniae and hCAP18/LL-37 concentrations in cell supernatants were measured at 8 hours. In panels (B), (D), (E) and (H) data shown as mean (+/- sem) and analyzed by one-way ANOVA with Bonferroni’s post-test. For human sputum analyses in (A) and (F) data are shown as median (IQR) and analyzed by Mann Whitney U test. In (C) and (G), correlation analysis used was nonparametric (Spearman’s correlation). Animal experiments comprise n=5-8 mice/group, representative of at least two independent experiments. BEAS2B experiments comprise n=4 independent experiments. n.s. non-significant *p<0.05 **p<0.01 ***p<0.001