PMC

Effect of GG, AR, GG plus AR, GA, and TN on CXCL2, IL-17A, CXCL1, and TNF-α in BALF and SDMA production in serum of COPD model mice. Mice were challenged by intratracheal injection of CFD, and then treated with GG, AR, GG plus AR, GA, and TN over a period of 12 days. The levels of CXCL2 (A), IL-17A (B), CXCL1 (C), and TNF-α (D) in BAL fluid and SDMA (E) in serum were determined by ELISA. Normal: normal group; Con.: CFD, CFD-induced COPD model group; Dexa.: CFD solution and administrated with dexamethasone 3 mg/kg group; GG 100: CFD solution and administrated with GG extract 100 mg/kg group; AR 100: CFD solution and administrated with AR extract 100 mg/kg group; GG + AR 50: CFD solution and administrated with GG plus AR extract 50 mg/kg group; GG + AR 100: CFD solution and administrated with GG plus AR extract 100 mg/kg group; GG + AR 200: CFD solution and administrated with GG plus AR extract 200 mg/kg group; GG+AR 100*(trial product): CFD solution and administrated with GG plus AR (trial product) 100 mg/kg group; GA 10: CFD solution and administrated with GA 10 mg/kg group; TN 10: CFD solution and administrated with TN 10 mg/kg group. The statistical significance of differences between control and treatment groups were assessed by ANOVA and Duncan’s multiple comparison test. Data represent the mean ± SEM of 8 independent experiments. (# P < 0.05, ## P < 0.01, ### P < 0.001, significantly different from the value of normal group. * P < 0.05, ** P < 0.01, and *** P < 0.001 significantly different from the value of control group).

Quantifying contact response due to combinations of genetic perturbations. (A) The CFD at which cells exhibit moderate sliding efficiency was quantified. Arrows indicate that the CFD for MCF-10A cells and MDA-MB-231 cells is >35 μm and <5 μm, respectively. Knockdown of E-cadherin (10A-shEcad) reduces the CFD, whereas the expression of exogenous E-cadherin in 231 cells (231-Ecad) increases CFD. Downregulation of PARD3 and activation of ErbB2 (10A.B2-shPAR3 + AP) reduces the CFD, but either perturbation alone has no effect on CFD relative to the control (10A.B2-shGFP + Veh). (B) The effect of TGF-β treatment along with perturbations in PARD3 and ErbB2 on the CFD. Treatment of cells with TGF-β reduces the value of CFD compared to untreated cells. Additionally, TGF-β treatment has a superimposable effect on reducing the CFD when combined with single and/or multiple genetic perturbations.

Inhibitory effect of GG, AR, GG plus AR, GA, and TN on STAT3 transcription factor using immunofluorescence analysis in lung tissues of COPD model mice. Mice were challenged by intratracheal injection of CFD, and then treated with GG, AR, GG plus AR, GA, and TN over a period of 12 days. The expression of STAT3 transcription factor in lung tissues was determined by immunofluorescence staining (A). The mean of fluorescence intensity quantified from images was obtained from 3 independent experiments using Image J software (B). Normal: normal group; Con.: CFD, CFD-induced COPD model group; Dexa.: CFD solution and administrated with dexamethasone 3 mg/kg group; GG 100: CFD solution and administrated with GG extract 100 mg/kg group; AR 100: CFD solution and administrated with AR extract 100 mg/kg group; GG+AR 50: CFD solution and administrated with GG plus AR extract 50 mg/kg group; GG + AR 100: CFD solution and administrated with GG plus AR extract 100 mg/kg group; GG + AR 200: CFD solution and administrated with GG plus AR extract 200 mg/kg group; GG + AR 100*(trial product): CFD solution and administrated with GG plus AR (trial product) 100 mg/kg group; GA 10: CFD solution and administrated with GA 10 mg/kg group; TN 10: CFD solution and administrated with TN 10 mg/kg group. The statistical significance of differences between control and treatment groups were assessed by ANOVA and Duncan’s multiple comparison test. Data represent the mean ± SEM of 8 independent experiments. (### P < 0.001, significantly different from the value of normal group. * P < 0.05 and ** P < 0.01 significantly different from the value of control group).

Effects of GG, AR, GG plus AR, GA, and TN on CXCL2, IL-17A, CXCL1, MUC5AC, IL-6, TNF-α NOS-II, and TRPV1 mRNA gene expression in the lung tissue of CFD-induced COPD model mice. CXCL2 (A), IL-17A (B), CXCL1 (C), MUC5AC (D), IL-6 (E), TNF-α (F), NOS-II (G), and TRPV1 (H) mRNA levels were measured in mouse lung tissue of each groups. Normal: normal group; Con.: CFD, CFD-induced COPD model group; Dexa.: CFD solution and administrated with dexamethasone 3 mg/kg group; GG 100: CFD solution and administrated with GG extract 100 mg/kg group; AR 100: CFD solution and administrated with AR extract 100 mg/kg group; GG + AR 50: CFD solution and administrated with GG plus AR extract 50 mg/kg group; GG + AR 100: CFD solution and administrated with GG plus AR extract 100 mg/kg group; GG + AR 200: CFD solution and administrated with GG plus AR extract 200 mg/kg group; GG + AR 100* (trial product): CFD solution and administrated with GG plus AR (trial product) 100 mg/kg group; GA 10: CFD solution and administrated with GA 10 mg/kg group; TN 10: CFD solution and administrated with TN 10 mg/kg group. The statistical significance of differences between control and treatment groups were assessed by ANOVA and Duncan’s multiple comparison test. Data represent the mean ± SEM of 8 independent experiments. (## P < 0.01, ### P < 0.001, significantly different from the value of normal group. * P < 0.05, ** P < 0.01, and *** P < 0.001 significantly different from the value of control group).