Activation of MAP kinases during progression of radiation-induced pneumonitis in rats.
Radiation-induced pneumonitis is closely associated with the interplay of various stress-activated signals and immune responses related to the progression of lung injury. Mitogen-activated protein (MAP) kinase pathways play critical roles in the progression of inflammation via a cellular damage. Here, we examined the regional distribution of phosphorylated MAP kinases (p-JNK, p-ERK, and p-p38) in the progression of pneumonitis after exposure of a single dose irradiation with 10 Gy for 0, 4, and 8 weeks in rats. Also, we identified positive cells for these kinases using specific cell-type markers related to inflammation and type II pneumocyte. p-JNK was present abundantly in activated macrophages, CD8(+)T-cells, peribronchiolar smooth muscle cells, and weakly type II pneumocytes at 4 weeks or 8 weeks after irradiation. p-p38 and p-ERK was predominantly expressed in macrophages, CD4(+) T-cells, fibrotic cells as well as present in various lung parenchymal cells including alveolar epithelial cells and type II pneumocytes. In conclusion, it is considered that MAP kinase pathways play a pivotal role in early damage of residual cells as well as in the long-term regulation of distinct inflammatory cells during the progression of radiation-induced pneumonitis.
Ryu
Si-Yun
SY
Department of Veterinary Medicine and Research Institute of Veterinary Science, College of Veterinary Medicine, Chungnam National University, Daejeon, 305-764, Korea.
Do
Sun-Hee
SH
Chung
Jae-Yong
JY
Kim
Tae-Hwan
TH
Kim
Sung-Ho
SH
Choi
Cheol-Yong
CY
Jeong
Kyu-Shik
KS
Park
Sang-Joon
SJ
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology; D018414:CD8-Positive T-Lymphocytes / Q000201:enzymology; D004195:Disease Models, Animal; D018450:Disease Progression; D004789:Enzyme Activation / Q000528:radiation effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D015151:Immunoblotting; D007150:Immunohistochemistry; D008168:Lung / Q000201:enzymology / Q000473:pathology / Q000528:radiation effects*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D008297:Male; D011833:Radiation Injuries, Experimental / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D017564:Radiation Pneumonitis / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4