Nuclear factor-kappa B in signal conduction of protein kinase C in T lymphocytes from an asthmatic guinea pig model.
OBJECTIVE
To explore the role of nuclear factor-kappa B (NF-kappa B) in the signal conduction of protein kinase C (PKC) regulated proliferation, apoptosis and expression of Th2 cytokines -- interleukin-4 (IL-4) and interleukin-5 (IL-5) of T lymphocytes in the bronchial alveolus lavage fluid (BALF).


METHODS
T lymphocytes were isolated and purified from BALF of asthmatic guinea pigs in normal and asthmatic groups, and were stimulated with PKC agitator phorbol 12-myristate 13-acetate (PMA) and NF-kappa B inhibitor pyrrolidine dithiocarbamate (PDTC), respectively. The expressions of NF-kappa B, IL-4 and IL-5 mRNA and protein, the proliferation and apoptosis of T lymphocytes were observed by immunohistochemistry, in situ hybridization, ELISA, MTT and TUNEL, respectively.


RESULTS
The activation of NF-kappa B, proliferation response, and expression of IL-4 and IL-5 mRNA and protein in T lymphocytes stimulated by PMA were significantly higher than those of their blank control (P < 0.01), while those indexes of T lymphocytes stimulated by PMA and PDTC simultaneously were significantly lower than those stimulated by PMA alone (P < 0.01). The apoptotic index of T lymphocytes stimulated with PMA were significantly lower than that of their blank control (P < 0.01), and the apoptotic index of asthmatic guinea pig T lymphocytes stimulated with PMA and PDTC simultaneously were significantly higher than that stimulated by PMA alone (P < 0.01). The significant positive correlations were found between the activation of NF-kappa B and the proliferation (r = 0.64, P < 0.001), and the expression of IL-4 and IL-5 mRNA and protein of T lymphocytes, respectively (r = 0.55 - 0.68, P < 0.001). There was also significant negative correlation between the activation of NF-kappa B and apoptosis of T lymphocytes (r = 0.62, P < 0.001).


CONCLUSIONS
NF-kappa B may participate in the signal conduction of PKC regulated proliferation, apoptosis and expression of IL-4 and IL-5 of T lymphocytes in asthma. The activation of NF-kappa B in PKC signal conduction pathway of T lymphocytes may play an important role in the pathogenesis of asthma.
Xiong
Weining
W
Department of Respiratory Medicine, Tongji Hodpital Affiliated to Tongji Medical College, Huazhong University of Science and Techonology, Wuhan 430030, China. xiongweining@263.net
Xu
Yongjian
Y
Zhang
Zhenxiang
Z
Wang
Xiaoyang
X
Mo
Biwen
B
Fu
Juan
J
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001249:Asthma / Q000378:metabolism* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D004195:Disease Models, Animal; D006168:Guinea Pigs; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D015848:Interleukin-5 / Q000235:genetics / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D011759:Pyrrolidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013859:Thiocarbamates / Q000494:pharmacology
D015848:Interleukin-5; D016328:NF-kappa B; D011759:Pyrrolidines; D012333:RNA, Messenger; D013859:Thiocarbamates; D015847:Interleukin-4; C020972:pyrrolidine dithiocarbamic acid; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate