PMID- 18466678
OWN - NLM
STAT- MEDLINE
DCOM- 20080708
LR  - 20151119
IS  - 0366-6999 (Print)
IS  - 0366-6999 (Linking)
VI  - 121
IP  - 7
DP  - 2008 Apr 5
TI  - Inhibition of tumor necrosis factor-alpha reduces alveolar septal cell apoptosis 
      in passive smoking rats.
PG  - 597-601
AB  - BACKGROUND: Recent studies have revealed that lung cell apoptosis plays an 
      important role in pathogenesis of cigarette-induced chronic obstructive pulmonary 
      disease (COPD). Tumor necrosis factor alpha (TNF-alpha) is one of the most 
      important cytokines which are involved in COPD. This study aimed at investigating 
      the influence of its inhibitor, recombinant human necrosis factor-alpha receptor 
      II:IgG Fc fusion protein (rhTNFR:Fc) on alveolar septal cell apoptosis in passive 
      smoking rats. METHODS: Forty-eight rats were randomly divided into a normal 
      control group, a passive smoking group, an rhTNFR:Fc intervention group and a 
      sham intervention group. The passive smoking rats were treated by exposure to 
      cigarette smoking daily for 80 days. After smoking for one month the rhTNFR:Fc 
      intervention group was treated with rhTNFR:Fc by subcutaneous injection, the sham 
      intervention group injected subcutaneously with a neutral preparation (normal 
      saline 0.1 ml, manicol 0.8 ml, cane sugar 0.2 mg, Tris 0.024 mg as a control. 
      Lung function was determined and the levels of TNF-alpha in serum and 
      broncho-alveolar lavage fluid (BALF) were measured with enzyme-linked 
      immunosorbnent assay (ELISA). Lung tissue sections stained by hematoxylin and 
      eosin (HE) were observed for study of morphological alternations. Mean linear 
      intercept (MLI) and mean alveolar numbers (MAN) were measured and the terminal 
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method was 
      carried out to determine the percentage of positive cells and distribution of 
      apoptotic cells. RESULTS: Increased MLI and decreased MAN were found in the 
      passive smoking group compared with both the normal control group and the 
      rhTNFR:Fc intervention group (P < 0.05). Forced expiratory volume in 0.3 second 
      (FEV 0.3)/forced vital capacity (FVC) and peak expiratory flow (PEF) were lower 
      in the passive smoking group than that in the normal control group (P < 0.05). 
      Compared with the sham intervention group, FEV 0.3/FVC and PEF increased in the 
      rhTNFR:Fc intervention group (P < 0.05). The levels of TNF-alpha in serum were 
      higher in the passive smoking group than that in the normal control group (P < 
      0.05) and rhTNFR:Fc intervention group (P < 0.05). Significant differences were 
      found between the levels of TNF-alpha in the serum of the rhTNFR:Fc intervention 
      group and sham intervention group (P < 0.05). The levels of TNF-alpha in BALF 
      were higher in the passive smoking group than that in the normal control group (P 
      < 0.05), but no significant differences of TNF-alpha levels in BALF were found 
      between the passive smoking group and rhTNFR:Fc intervention group. The number of 
      TUNEL positive cells in alveolar septa was significantly increased in the passive 
      smoking group as compared with the normal control group and the rhTNFR:Fc 
      intervention group (P < 0.05). CONCLUSION: This study provides preliminary 
      evidence that rhTNFR:Fc may interfere with TNF-alpha and reduce alveolar septal 
      apoptosis in smoking rats.
FAU - Zhang, Cheng
AU  - Zhang C
AD  - Department of Respiratory Medicine, Second Xiangya Hospital of Central-South 
      University, Changsha, Hunan 410011, China.
FAU - Cai, Shan
AU  - Cai S
FAU - Chen, Ping
AU  - Chen P
FAU - Chen, Jian-bo
AU  - Chen JB
FAU - Wu, Jie
AU  - Wu J
FAU - Wu, Shang-jie
AU  - Wu SJ
FAU - Zhou, Rui
AU  - Zhou R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - China
TA  - Chin Med J (Engl)
JT  - Chinese medical journal
JID - 7513795
RN  - 0 (Immunoglobulin G)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Tobacco Smoke Pollution)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - OP401G7OJC (Etanercept)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Bronchoalveolar Lavage Fluid/chemistry
MH  - Etanercept
MH  - Forced Expiratory Volume
MH  - Immunoglobulin G/*pharmacology
MH  - Male
MH  - Pulmonary Alveoli/*pathology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Tumor Necrosis Factor
MH  - Recombinant Fusion Proteins/*pharmacology
MH  - *Tobacco Smoke Pollution
MH  - Tumor Necrosis Factor-alpha/analysis/*antagonists & inhibitors
EDAT- 2008/05/10 09:00
MHDA- 2008/07/09 09:00
CRDT- 2008/05/10 09:00
PHST- 2008/05/10 09:00 [pubmed]
PHST- 2008/07/09 09:00 [medline]
PHST- 2008/05/10 09:00 [entrez]
PST - ppublish
SO  - Chin Med J (Engl). 2008 Apr 5;121(7):597-601.