Role of extracellular signal-regulated kinase in regulating expression of interleukin 13 in lymphocytes from an asthmatic rat model.
BACKGROUND
The extracellular signal-regulated kinase (ERK) is widely expressed in mammal cells and involved in airway proliferation and remodeling in asthma. In this study, we intend to explore the role of ERK in the expression of the Th2 cytokine, interleukin 13 (IL-13) in lymphocytes in asthma.


METHODS
Forty Sprague-Dawley rats were randomly divided into two groups: normal control and asthmatic groups. Peripheral blood lymphocytes were isolated and purified from the blood of each rat and divided into five groups: control, asthmatic lymphocytes, asthmatic cells stimulated with ERK activator epidermal growth factor (EGF), or with ERK inhibitor PD98059, or with EGF and PD98059 together. The expression of phosphorylated-ERK (p-ERK) was observed by immunocytochemical staining, the expression of ERK mRNA was determined by reverse transcriptase-PCR, IL-13 protein in supernatants was measured by ELISA.


RESULTS
(1) The ERK mRNA level and the percentage of cells with p-ERK in lymphocytes from asthmatic rats were significantly higher than those in normal controls, and were significantly increased by EGF administration. This effect of EGF was significantly inhibited by PD98059 pretreatment. (2) IL-13 protein in supernatants of asthmatic lymphocytes was higher than that produced by normal control lymphocytes, and was significantly increased by EGF treatment. This EGF effect was partly blocked by PD98059 pretreatment. (3) There was a significant positive correlation between the percentage of cells with p-ERK in peripheral blood lymphocytes and IL-13 protein in supernatants of lymphocytes from asthmatic rats.


CONCLUSIONS
In asthma the ERK expression and activation levels were increased, as was the protein level of IL-13. The ERK signaling pathway may be involved in the increased expression of the Th2 cytokine IL-13 in asthma.
Li
Yuan-Yuan
YY
Department of Respiratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
Liu
Xian-Sheng
XS
Liu
Chang
C
Xu
Yong-Jian
YJ
Xiong
Wei-Ning
WN
D000818:Animals; D001249:Asthma / Q000378:metabolism*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D007150:Immunohistochemistry; D018793:Interleukin-13 / Q000378:metabolism*; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D005419:Flavonoids; D018793:Interleukin-13; D048049:Extracellular Signal-Regulated MAP Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one