[The effect of phosphoinositide-3-kinase and signal transducer and activator of transcription-6 on the proliferation of T lymphocytes in bronchial asthma].
OBJECTIVE
To investigate the effect of phosphoinositide-3-kinase (PI(3)K) and signal transducer and activator of transcription-6 (STAT(6)) on the proliferation of CD(4)(+) and CD(8)(+) T lymphocytes in bronchial asthma.


METHODS
CD(4)(+) and CD(8)(+) T lymphocytes of 15 asthmatic patients or 15 healthy control subjects were cultured in vitro from August of 2004 to February of 2005. The T lymphocytes of asthmatic patients were divided into four groups and stimulated with or without 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002) and IFN-gamma. The four groups included a control group (group A), the LY294002 group (group B), IFN-gamma group (group C) and LY294002 + IFN-gamma group (group D). The cell cycle phases and the expression of cell cycle proteins (P27kip1, Cyclin D, Cyclin E), PI(3)K and STAT(6) were analyzed by flow cytometry.


RESULTS
(1) The percentage of G(0)/G(1) phase, the expression rate of P27kip1 in CD(4)(+) and CD(8)(+) T lymphocytes from asthmatic patients were 82.0%, 44.6%, 13.2%, 4.5%; and those from the control group were 99.0%, 100.0%, 47.2%, 46.3%, respectively; the difference was significant between the two groups (Z value were 3.54, 4.23, 3.09 and 2.51, all P < 0.05). The percentage of S phase, the expression rate of Cyclin E, PI(3)K and STAT(6) in CD(4)(+) and CD(8)(+) T lymphocytes from the asthmatic patients were 18.0%, 51.7%, 7.9%, 9.3%, 7.6%, 8.7%, 8.2%, 6.3%; and those from the control group were 0.2%, 0.0%, 3.7%, 3.5%, 3.3%, 3.4%, 1.9%, 2.4%, respectively; there were significant differences between the two groups (Z value were 2.88, 4.61, 1.95, 2.06, 2.51, 2.32, 4.38 and 2.22, all P < 0.05). (2) The percentage of G(0)/G(1) phase, S phase, the expression rate of Cyclin D, Cyclin E in CD(4)(+) T lymphocytes of B group were 95.6%, 1.9%, 13.3% and 3.1%; and those of A group were 82.0%, 18.0%, 35.0%, 7.9%; there were significant differences between the two groups (Z value were 2.04, 2.23, 2.78 and 1.99, all P < 0.05). The percentage of S phase, the expression rate of Cyclin E in CD(8)(+) T lymphocytes of B group were 1.0% and 4.1%; and those of A group were 51.7% and 9.3%; there were significant differences between the two groups (Z value were 3.06 and 2.56, all P < 0.05). The percentage of G(0)/G(1) phase, S phase, the expression rate of P27kip1 in CD(4)(+) T lymphocyte of C group were 94.0%, 1.5%, 46.1%; and those of A group were 82.0%, 18.0%, 13.2%; there were significant differences between the two groups (Z value were 2.17, 2.54 and 2.81, all P < 0.05). The percentage of S phase, the expression rate of P27kip1 in CD(8)(+) T lymphocyte of C group were 10.8% and 23.1%; and those of A group were 51.7% and 4.5%; there were significant differences between the two groups (Z value were 2.67 and 2.05, all P < 0.05). The percentage of G(0)/G(1) phase, S phase, the expression rate of P27kip1, Cyclin D in CD(4)(+) T lymphocytes of D group were 97.0%, 0.0%, 40.4%, 21.5%; and those of A group were 82.0%, 18.0%, 13.2%, 35.0%; there were significant differences between the two groups (Z value were 2.73, 2.79, 2.56 and 2.10, all P < 0.05). The percentage of S phase, the expression rate of P27kip1 in CD(8)(+) T lymphocytes of D group were 92.1% and 1.7%; and those of A group were 44.6% and 51.7%; there were significant differences between the two groups (Z were 2.22 and 3.12, all P < 0.05).


CONCLUSIONS
PI(3)K and STAT(6) may be new therapeutic targets for the treatment of asthma. Further studies are necessary to explore the relationship between PI(3)K and JAK1-STAT(6) signal pathway during the enhancement of CD(4)(+) T or CD(8)(+) T lymphocyte proliferation in bronchial asthma.
Qiu
Chen
C
Department of Respiratory Medicine, Second College of Clinical Medicine of Jinan University, Shenzhen 518020, China.
Feng
Meng-jie
MJ
Li
Fu-rong
FR
Chen
Cai-xia
CX
Lai
Ying-jun
YJ
D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D050800:STAT6 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult
D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D019869:Phosphatidylinositol 3-Kinases