An Experimental Study on the Role of Nuclear Factor-κB in the Signal Conduction of Protein Kinase C Regulating the Proliferation and Apoptosis of T Lymphocytes in Asthma
To explore the role of nuclear factor-κB(NF-κB) in the signal pathway of protein kinase C (PKC) regulating the proliferation and apoptosis of T lymphocytes in asthma. T lymphocytes were isolated from the asthmatic model of guinea pigs and the asthmatic patients. Either the T cells stimulated with PMA alone or those stimulated with PMA together with pyrrolidine dithiocarbamate (PDTC) were incubated for 1 and 24?h. The proliferation of and the presence of NF-κB in the cells incubated for 1?h were observed by MTT and immunohistochemical staining, respectively. And the cells incubated for 24?h were observed for the apoptosis by TUNEL. All the assays were paralleled with controls, and all the data were analyzedstatistically with the software SAS. The percentage of cells of nuclear positive staining of NF-κB and the proliferation of T lymphocytes from asthmatic guinea pigs and asthmatic patients stimulated with PMA were significantly higher than those of T lymphocytes from asthmatic guinea pigs and asthmatic patients stimulated without PMA respectively (P0.01) and those of T lymphocytes from normal control guinea pigs and normal control persons stimulated with PMA respectively (P0.01), and were significantly reduced by PDTC (P0.01). The apoptosis index of T lymphocytes from asthmatic guinea pigs and asthmatic patients stimulated with PMA were significantly lower than those of T lymphocytes from asthmatic guinea pigs and asthmatic patients stimulated without PMA respectively (P0.01) and those of T lymphocytes from normal control guinea pigs and normal control persons stimulated with PMA respectively (P0.01), and were significantly induced by PDTC (P0.01). There were good positive correlation between the percentage of cells of nuclear staining of NF-κB of T lymphocytes and the proliferation of T lymphocytes (r=0.51-0.72, P0.001), and also good negative correlation between the percentage of cells of nuclear staining of NF-κB and the apoptosis index of T lymphocytes (r=-0.55-0.71, P0.001, respectively). It concludes that the active PKC of asthmatic T lymphocytes promoting the proliferation and inhibiting the apoptosis of T lymphocytes may be mediated by activating NF-κB, the activation of PKC-NF-κB signal pathway of T lymphocytes NF-κB may play an important role in the pathogenesis of asthma.