Amezaga M A, Bazzoni F, Sorio C, Rossi F, Cassatella M A
Institute of General Pathology, University of Verona, Italy.
Blood. 1992 Feb 1;79(3):735-44.
We recently showed that mRNA levels coding the high-affinity Fc gamma receptor for IgG (Fc gamma R-I, CD64) and two of the components of the phagocytic superoxide anion-generating system--the heavy-chain subunit of cytochrome b558 (gp91-phox) and the 47-Kd cytosolic factor (p47-phox)--are modulated by interferon gamma (IFN-gamma). In this study, we examined whether dexamethasone (DEX) affects gp91-phox and p47-phox mRNA expression of human polymorphonuclear leukocytes (PMN), treated or not with IFN-gamma. We also investigated whether staurosporine, a general inhibitor of protein kinases, influences gp91-phox, p47-phox, and Fc gamma R-I gene expression in PMN treated with or without IFN-gamma. We found that (1) gp91-phox mRNA steady-state levels, expressed in control or IFN-gamma-treated PMN, were significantly inhibited, in a dose-dependent fashion, by both DEX and staurosporine; (2) p47-phox mRNA steady-state levels, expressed in control or IFN-gamma-treated PMN, were not influenced by DEX, but were markedly depressed by staurosporine; (3) no changes of spectrophotometric cytochrome b558 were found in PMN treated for up to 20 hours with the inhibitors, regardless of the presence of IFN-gamma; (4) both DEX and staurosporine dose-dependently inhibited IFN-gamma-induced Fc gamma R-I mRNA and protein expression; and (5) stability of gp91-phox and Fc gamma R-I messages in IFN-gamma-treated PMN was not altered by the presence of DEX. Our results demonstrate that gp91-phox, p47-phox, and Fc gamma R-I gene expression of PMN is governed by specific and independent biochemical pathways. Moreover, IFN-gamma activates different signal transduction pathways to modulate mRNA expression of gp91-phox, p47-phox, and Fc gamma R-I.
我们最近发现，编码IgG高亲和力Fcγ受体（FcγR-I，CD64）以及吞噬细胞超氧阴离子生成系统的两个组分——细胞色素b558重链亚基（gp91-phox）和47-Kd胞质因子（p47-phox）的mRNA水平，受到干扰素γ（IFN-γ）的调节。在本研究中，我们检测了地塞米松（DEX）是否会影响经IFN-γ处理或未处理的人多形核白细胞（PMN）中gp91-phox和p47-phox的mRNA表达。我们还研究了蛋白激酶的通用抑制剂星形孢菌素，是否会影响经IFN-γ处理或未处理的PMN中gp91-phox、p47-phox和FcγR-I基因的表达。我们发现：（1）在对照或IFN-γ处理的PMN中表达的gp91-phox mRNA稳态水平，均受到DEX和星形孢菌素的显著抑制，且呈剂量依赖性；（2）在对照或IFN-γ处理的PMN中表达的p47-phox mRNA稳态水平，不受DEX影响，但被星形孢菌素显著降低；（3）用抑制剂处理长达20小时的PMN中，无论是否存在IFN-γ，分光光度法检测的细胞色素b558均未发现变化；（4）DEX和星形孢菌素均呈剂量依赖性地抑制IFN-γ诱导的FcγR-I mRNA和蛋白表达；（且5）DEX的存在并未改变IFN-γ处理的PMN中gp91-phox和FcγR-I信息的稳定性。我们的结果表明，PMN的gp91-phox、p47-phox和FcγR-I基因表达受特定且独立的生化途径调控。此外，IFN-γ激活不同的信号转导途径来调节gp91-phox、p47-phox和FcγR-I的mRNA表达。
