[Regulatory function of nuclear factor kappa B on lymphocyte proliferation and apoptosis in bronchial asthmatic rats and effect of triptolide on the regulation].
OBJECTIVE
To investigate whether nuclear factor kappa B (NF-kappa B) participates in the regulatory function of lymphocyte proliferation and apoptosis in bronchial asthma and whether the regulatory effect of triptolide on lymphocyte proliferation and apoptosis is conducted through NF-kappa B.


METHODS
Intervention with dexamethasone, triptolide and PDTC, a NF-kappa B inhibitor, were used to treat astmatic rats respectively. Pathological examination, airway response were determined, the NF-kappa B P65 expression in lung tissue and splenic lymphocytes by immunofluorescent assay were adopted, proliferative cell nuclear antigen (PCNA) in splenic lymphocytes was measured by immunohistochemistry, apoptosis of splenic lymphocytes were monitored by flow cytometry and NF-kappa B activity was investigated by electrophoresis mobility shift assay (EMSA).


RESULTS
The nuclear expression and DNA binding activity of lung tissue and splenic lymphocytes in asthmatic rats were all significantly higher than those in the control (all P < 0.05), so was the proliferation rate of splenic lymphocytes (P < 0.05), while the apoptosis rate was much lower than that of normal control (P < 0.05). Administration of PDTC could reduce the up-regulated expression and activity of NF-kappa B, the proliferation of splenic lymphocytes lowered, while the apoptosis increased. NF-kappa B activity showed an obviously positive correlation with proliferation of splenic lymphocytes (r = 0.89, P < 0.05) and a significantly negative correlation with apoptosis rate (r = -0.54, P < 0.05). After asthmatic rats had been treated with triptolide in vivo, the NF-kappa B nuclear expression and activity in airway and splenic lymphocytes, as well as the proliferation rate of splenic lymphocytes all lowered significantly (all P < 0.05), the apoptosis rate increased significantly (P < 0.05), at the same time, the inflammatory cell infiltration and high reactivity of airway were significantly alleviated (both P < 0.05). There were obviously positive correlation between the amount of airway eosinophils and reactivity with activity of NF-kappa B (r = 0.79 and r = 0.68, P < 0.05), which indicated that the effect of triptolide was not significantly different from that of dexamethasone (P > 0.05).


CONCLUSIONS
(1) NF-kappa B participates the formation of airway inflammation and hyper-reactivity in asthmatic rats by positive regulation on proliferation and negative regulation on apoptosis of lymphocytes. (2) Triptolide reduces airway inflammation by way of inhibiting NF-kappa B, and further inhibiting the proliferation of lymphocytes, so that to give full play of the role of anti-asthmatic airway inflammatory agents. Whether the molecular mechanism of triptolide in inhibiting NF-kappa B simulates that of glucocorticoid needs further studying.
Zhang
Ning
N
Department of Respiratory Medicine, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030. nzhang@mails.tjmu.edu.cn
Xu
Yong-jian
YJ
Zhang
Zhen-xiang
ZX
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001249:Asthma / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D004224:Diterpenes / Q000494:pharmacology*; D004852:Epoxy Compounds; D008168:Lung / Q000378:metabolism; D008214:Lymphocytes / Q000473:pathology*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D010616:Phenanthrenes / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D051996:Transcription Factor RelA
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004224:Diterpenes; D004852:Epoxy Compounds; D016328:NF-kappa B; D010616:Phenanthrenes; D051996:Transcription Factor RelA; C001899:triptolide; D003907:Dexamethasone