Downregulation of secretory leukocyte proteinase inhibitor in chronic obstructive lung disease: the role of TGF-beta/Smads signaling pathways.
BACKGROUND
Secretory leukocyte proteinase inhibitor (SLPI) is an important antileukoprotease in airway. The aim of the present study was to explore the expression of SLPI in the bronchi and lung tissues of chronic obstructive pulmonary disease (COPD) models and the regulative mechanism by transforming growth factor (TGF)beta(1)/Smads signal pathway in bronchial epithelial cell.


METHODS
COPD rat model was established and was treated with or without TGFbeta1 monoclonal antibody. Spirometry was conducted, and expressions of TGFbeta(1), Smad4 and SLPI were examined by immunohistochemistry and reverse-transcription polymerase chain reaction (RT-PCR), respectively. The normal human bronchial epithelial cell (NHBE) was cultured, preincubated with or without siRNA (Smad4), and then stimulated with TGFbeta(1). Expressions of Smad4 and SLPI were detected by immunocytochemistry, Western blot and RT-PCR, respectively.


RESULTS
As compared with the model group, after treatment with TGFbeta(1) monoclonal antibody, peak expiratory flow (PEF), forced expiratory volume in 0.3 sec (FEV(0.3)) and FEV(0.3)/forced vital capacity (FVC) in the TGFbeta(1) monoclonal antibody intervention group were all significantly improved. Expression of SLPI was also improved, but expression of Smad4 was significantly decreased. Expression of SLPI in NHBE cells was inhibited by TGFbeta(1) both at the mRNA level and the protein level. Furthermore, effect of TGFbeta(1)-inhibited expression of SLPI in NHBE cells was disengaged by siRNA (Smad4) both at the mRNA level and the protein level.


CONCLUSIONS
Decreased expression of SLPI in the COPD rat model may be mainly caused by the increased expression of TGFbeta(1), and this process is probably related to the activation of Smads signal pathway.
Luo
Bai-Ling
BL
Department of Respiratory Medicine, Xiangya Hospital of Central South University, Hunan Province, Changsha, PR China. blluo181@yahoo.com.cn
Niu
Rui-Chao
RC
Feng
Jun-Tao
JT
Hu
Cheng-Ping
CP
Xie
Xiao-Yun
XY
Ma
Li-Juan
LJ
D000818:Animals; D001980:Bronchi / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008168:Lung / Q000473:pathology / Q000503:physiopathology; D008297:Male; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D020545:Respiratory Mucosa / Q000473:pathology; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000378:metabolism*; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D053481:Secretory Leukocyte Peptidase Inhibitor; C506816:Slpi protein, rat; D051785:Smad Proteins; D016212:Transforming Growth Factor beta