MAP kinase activation and apoptosis in lung tissues from patients with idiopathic pulmonary fibrosis

Journal of Pathology - Tập 198 Số 3 - Trang 388-396 - 2002
Koichiro Yoshida1, Kazuyoshi Kuwano1, Naoki Hagimoto1, Junji Uchino2, Tokuji Matsuba1, Masaki Fujita1, Ichiro Inoshima1, Nobuyuki Hara1
1Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
2Fourth Department of Internal Medicine, Fukuoka University, Fukuoka, Japan

Tóm tắt

AbstractThree major MAP kinases (MAPKs), including extracellular signal‐regulated kinase (ERK), c‐jun N‐terminal kinase (JNK), and p38 kinase (p38 MAPK), are involved in the regulation of lung inflammation and injury. This study investigated whether MAPKs are activated and associated with lung injury in lung tissues from patients with idiopathic pulmonary fibrosis (IPF). The expression of the active ERK, JNK, and p38 MAPK was examined using western blot analysis and immunohistochemistry and apoptosis was also examined by the TUNEL method, in lung tissues from ten patients with IPF obtained by thoracoscopic biopsy and in eight normal lung parenchyma specimens obtained by lobectomy for lung cancer. Activated MAPKs are significantly increased in lung homogenates from patients with IPF compared with controls. Activated ERK in epithelial and endothelial cells, but not in fibroblasts or smooth muscle cells, was decreased, accompanied by the progression of fibrosis. Activated JNK in epithelial and endothelial cells, but not in fibroblasts, was increased, accompanied by the progression of fibrosis. Activated p38 MAPK in epithelial, endothelial, smooth muscle cells, and fibroblasts was increased at the intermediate stage of fibrosis, in which the TUNEL‐positive cells were predominantly detected. This is the first study to suggest that MAPKs may be associated with the regulation of inflammation and lung injury in IPF. Copyright © 2002 John Wiley & Sons, Ltd.

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Tài liệu tham khảo

Chang L, 2001, Mammalian MAP kinase signaling cascades, Science, 410, 37

10.1164/ajrccm.154.2.8756825

10.1002/(SICI)1097-4652(199908)180:2<158::AID-JCP3>3.0.CO;2-R

10.1164/ajrccm.161.2.ats3-00

Shin RW, 1991, Methods in laboratory investigation. Hydrated autoclave pretreatment enhances TAU. Immunoreactivity in formalin‐fixed normal and Alzheimer's disease brain tissues, Lab Invest, 64, 693

10.1136/jcp.41.4.467

10.1152/ajplung.1999.277.1.L159

10.1165/ajrcmb.20.1.2941

10.1016/S0092-8674(00)80294-9

10.1016/S0167-8140(98)00007-3

10.1016/S0091-6749(98)70311-2

10.1046/j.1365-2222.2000.00641.x

10.1016/S0002-9440(10)64570-1

10.1159/000024011

10.1006/excr.1998.4359

10.1182/blood.V95.10.3044

10.1006/bbrc.1996.5886

10.1073/pnas.90.18.8319

10.1006/bbrc.1998.9188

10.1164/ajrccm.163.1.2005069

10.1074/jbc.M909785199

10.1152/ajplung.2000.279.5.L895

10.1152/ajplung.2001.280.5.L1019

10.1164/ajrccm.161.3.9906059

10.1165/ajrcmb.23.1.4014

10.1016/S0002-9440(10)65061-4

10.1073/pnas.93.7.2774

10.1165/ajrcmb.20.4.3420

10.1002/eji.1830260505

10.1093/emboj/19.20.5418

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Journal of Pathology

Tập 198 Số 3

388-396

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