Characteristic comparison of three rat models induced by cigarette smoke or combined with LPS: to establish a suitable model for study of airway mucus hypersecretion in chronic obstructive pulmonary disease.
There is a need of in vivo COPD models for mucus hypersecretion study. The current study compared three rat models induced by cigarette smoke (CS) exposure alone or combined with pre- or post-treatment with lipopolysaccharide (LPS). Forty rats were randomly divided into the four following groups: control group, LPS + CS group (CS exposure for 4-wk combined with LPS pretreatment), CS group (CS exposure for 6-wk), CS + LPS group (CS exposure for 6-wk combined with LPS post-treatment). The results showed that both CS and CS + LPS groups had more severe pro-inflammatory cytokines secretion, inflammatory cells infiltration, and emphysema as compared to that in LPS + CS group animals. From the PAS staining sections, we found a remarkable hyperplasia of goblet-cell in epitheliums of trachea, bronchi, and bronchiole of all of three modeling groups, especially in CS and CS + LPS groups. From the western-blotting results, there were significant increase in the activities of NF-κB, AP-1, EGFR, TLR4, and MAPKs in all of three modeling groups, while HDAC2 activity was remarkably repressed in CS group only. Moreover, the expression and secretion of MUC5AC were exhibited significant increase in all of three modeling groups, which correlated well with the total transcription activity integration of NF-κB, AP-1, and HDAC2 (r = 0.946, p < 0.01). These results indicated that MUC5AC hypersecretion is consistent with activation of EGFR-AP-1/NF-κB and TLR4-AP-1/NF-κB signaling pathways, as well as repression of HDAC2 activity. Based on these results, we speculated that the 6-wk CS exposure rat model is a reliable COPD rat model, while the 6-wk CS exposure combined with LPS post-treatment rat model is a suitable COPD exacerbation model for mucus hypersecretion study.
Key Laboratory of Gene Engineering of the Ministry of Education, Guangdong Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-sen University, No. 135, Xingangxi Street, Guangzhou 510275, PR China.
Yi-Chu
YC
Nie
Hao
H
Wu
Pei-Bo
PB
Li
Yu-Long
YL
Luo
Chen-Chen
CC
Zhang
Jian-Gang
JG
Shen
Wei-Wei
WW
Su
D000818:Animals; D001980:Bronchi / Q000378:metabolism*; D004195:Disease Models, Animal; D066246:ErbB Receptors / Q000502:physiology; D056464:Histone Deacetylase 2 / Q000502:physiology; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D055271:Mucin 5AC / Q000235:genetics; D009093:Mucus / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana / Q000009:adverse effects*; D051197:Toll-Like Receptor 4 / Q000502:physiology; D051996:Transcription Factor RelA / Q000378:metabolism
D008070:Lipopolysaccharides; C524680:Muc5ac protein, rat; D055271:Mucin 5AC; D012906:Smoke; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D051996:Transcription Factor RelA; D066246:ErbB Receptors; C533426:Hdac2 protein, rat; D056464:Histone Deacetylase 2