| RRC ID |
77470
|
| 著者 |
Chen H, Zhang L, Jin Z, Jin E, Fujiwara M, Ghazizadeh M, Asoh S, Ohta S, Kawanami O.
|
| タイトル |
Anti-apoptotic PTD-FNK protein suppresses lipopolysaccharide-induced acute lung injury in rats.
|
| ジャーナル |
Exp Mol Pathol
|
| Abstract |
The present study was aimed at clarifying the effects of an anti-apoptotic protein for modulating symptoms in acute lung injury (ALI). From Bcl-x(L), a Bcl-2 family member, we constructed an artificial protein (FNK) and fused it with the protein transduction domain (PTD) of the HIV/Tat protein (PTD-FNK) to facilitate its permeation into cells. ALI was induced by intratracheal infusion of lipopolysaccharide (LPS) into Sprague-Dawley male rats. PTD-FNK was injected into the peritoneal cavity of the animals either 2 h before, or 3 h or 6 h after LPS challenge. All rats were sacrificed 24 h after the last treatment. Cell differential ratios and albumin concentration were estimated in bronchoalveolar lavage fluid. We examined histological change, myeloperoxidase activity, TUNEL assay, caspase-3/caspase-3-like activity and immunohistochemical reaction for caspase 3 (active form). In animals with PTD-FNK treatment, the albumin leakage was significantly attenuated with protection of tissue damage. Also, the apoptosis of alveolar wall cells was reduced by PTD-FNK treatment, while a total cell number and the neutrophil ratio were not changed. Human umbilical vein endothelial cells (HUVEC) and cells of an alveolar epithelial cell line (A549) were exposed to LPS or TNF-alpha with or without PTD-FNK treatment in vitro. Cell survival rates examined by trypan-blue exclusion assay were increased by PTD-FNK treatment in a concentration-dependent manner. Thus, PTD-FNK could play a protective role in ALI by suppressing apoptosis of alveolar epithelial cells and capillary endothelial cells despite of some effect on neutrophil activity.
|
| 巻・号 |
83(3)
|
| ページ |
377-84
|
| 公開日 |
2007-12-1
|
| DOI |
10.1016/j.yexmp.2007.08.016
|
| PII |
S0014-4800(07)00112-8
|
| PMID |
17959170
|
| MeSH |
Albumins / metabolism
Animals
Bronchoalveolar Lavage Fluid / cytology
Cell Line
Humans
Lipopolysaccharides / pharmacology*
Lung* / cytology
Lung* / drug effects
Lung* / pathology
Male
Rats
Rats, Sprague-Dawley
Recombinant Fusion Proteins / genetics
Recombinant Fusion Proteins / metabolism*
Respiratory Distress Syndrome / chemically induced*
bcl-X Protein / genetics
bcl-X Protein / metabolism*
tat Gene Products, Human Immunodeficiency Virus / genetics
tat Gene Products, Human Immunodeficiency Virus / metabolism
|
| IF |
2.28
|
| リソース情報 |
| ヒト・動物細胞 |
A549(RCB0098) |
