Kontny E, Ziółkowska M, Ryzewska A, Maśliński W
Department of Pathophysiology and Immunology, Institute of Rheumatology, Spartanska 1, Warsaw, 02-637, Poland.
Cytokine. 1999 Nov;11(11):839-48. doi: 10.1006/cyto.1998.0496.
The authors hypothesized that certain PKC isoforms play an important role in the induction of pro-inflammatory cytokine (TNF-alpha, IL-1beta, IL-6) synthesis. To test this hypothesis, the cytosol-to-membrane translocation of select PKC isoforms with tested cytokine production in human monocytes cultured in vitro was correlated. It is reported that in monocytes treated with phorbol ester (PMA), translocation of PKC isoforms alpha, betaII, delta and epsilon precede cytokine synthesis. Moreover, specific inhibition of PKC translocation that occurs in the presence of Calphostin C is reflected in downstream events: lack of MAP kinases phosphorylation, loss of DNA binding ability by AP-1 transcription factor, and the reduction of pro-inflammatory cytokine synthesis. Thus, the cytosol-to-membrane translocation of PKC isoforms alpha, betaII, delta and epsilon with the subsequent activation of: (1) MAP kinases; and (2) AP-1 transcription factor, may represent critical steps in the induction of signalling cascade leading to TNF-alpha, IL-1beta, IL-6 synthesis in human monocytes.
作者推测某些蛋白激酶C（PKC）亚型在促炎细胞因子（肿瘤坏死因子-α、白细胞介素-1β、白细胞介素-6）合成的诱导过程中发挥重要作用。为验证这一假设，研究了体外培养的人单核细胞中特定PKC亚型从胞质溶胶到细胞膜的转位与所检测的细胞因子产生之间的相关性。据报道，在用佛波酯（PMA）处理的单核细胞中，PKC亚型α、βII、δ和ε的转位先于细胞因子合成。此外，在钙泊三醇C存在的情况下发生的PKC转位的特异性抑制反映在下游事件中：丝裂原活化蛋白激酶（MAP激酶）磷酸化缺失、AP-1转录因子DNA结合能力丧失以及促炎细胞因子合成减少。因此，PKC亚型α、βII、δ和ε从胞质溶胶到细胞膜的转位以及随后（1）MAP激酶和（2）AP-1转录因子的激活，可能是诱导导致人单核细胞中肿瘤坏死因子-α、白细胞介素-1β、白细胞介素-6合成的信号级联反应的关键步骤。
