Akt pathway is required for oestrogen-mediated attenuation of lung injury in a rodent model of cerulein-induced acute pancreatitis.
BACKGROUND
The phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) is known to be an endogenous negative feedback or compensatory mechanism that serves to limit pro-inflammatory and chemotactic events in response to injury. The aim of this study is to elucidate whether Akt plays any role in 17β-estradiol (E2)-mediated attenuation of lung injury after acute pancreatitis (AP).


METHODS
Male Sprague-Dawley rats underwent cerulein-induced AP. Rats were treated with vehicle (cyclodextrin), E2 (1 mg/kg body weight [BW]), or E2 plus PI3K/Akt inhibitor Wortmannin (100 μg/kg BW) 1h after the onset of AP. At 8 h after sham operation or AP, various parameters were measured.


RESULTS
AP led to a significant decrease in lung Akt phosphorylation, which was associated with increased lung tissue myeloperoxidase (MPO) activity, wet-to-dry weight ratios, interleukin (IL)-6, tumor necrosis factor (TNF)-α, cytokine-induced neutrophil chemoattractant (CINC)-1, and CINC-3 levels. Administration of E2 after AP restored the AP-induced decrease in Akt phosphorylation and attenuated the increase in lung injury markers (MPO activity and wet-to dry weight ratios) and pro-inflammatory mediator production. The effects of E2 on the lung were abolished by co-administration of Wortmannin.


CONCLUSIONS
These results collectively suggest evidences that the Akt pathway seems to be required for E2-mediated protection of lung injury after AP.
Yang
Shang-Ju
SJ
Department of Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, 5, Fushing Street, Kweishan Shiang, Taoyuan 333, Taiwan.
Chen
Han-Ming
HM
Hsieh
Chi-Hsun
CH
Hsu
Jun-Te
JT
Yeh
Chun-Nan
CN
Yeh
Ta-Sen
TS
Hwang
Tsann-Long
TL
Jan
Yi-Yin
YY
Chen
Miin-Fu
MF
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002108:Ceruletide; D054360:Chemokine CXCL1 / Q000378:metabolism; D054426:Chemokine CXCL2 / Q000378:metabolism; D003505:Cyclodextrins / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D055370:Lung Injury / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D010195:Pancreatitis / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000077191:Wortmannin
D000730:Androstadienes; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; C513297:Cxcl1 protein, rat; C513296:Cxcl2 protein, rat; D003505:Cyclodextrins; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D004958:Estradiol; D002108:Ceruletide; D009195:Peroxidase; C111490:Akt3 protein, rat; D051057:Proto-Oncogene Proteins c-akt; D000077191:Wortmannin