[The effect of phosphoinositide-3-kinase and signal transducer and activator of transcription-6 on the proliferation of T lymphocytes in bronchial asthma].

ABSTRACT

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). CONCLUSION: 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.