Gibellini D, Zauli G, Re M C, Milani D, Furlini G, Caramelli E, Capitani S, La Placa M
Institute of Microbiology, University of Bologna, Italy.
Br J Haematol. 1994 Oct;88(2):261-7. doi: 10.1111/j.1365-2141.1994.tb05016.x.
In this study we evaluated the effect of human immunodeficiency virus type 1 (HIV-1) recombinant Tat protein on mRNA expression and protein synthesis of two inflammatory cytokines-interleukin-6 (IL-6) and transforming growth factor-beta 1 (TGF-beta 1)-by peripheral blood (PB) monocytes. Whereas maximal levels of IL-6 protein were recovered in PB monocyte culture supernatants after 24-48 h from the addition of 1 micrograms/ml of recombinant Tat, TGF-beta 1 showed a slower and progressive increase, reaching maximal levels only after 72-96 h of culture. Consistently, the analysis of the steady-state levels of mRNA showed a sharp increase of IL-6 mRNA expression after 24h of culture, with a slow decline thereafter. On the other hand, TGF-beta 1 mRNA expression showed a slow increase only after 72-96 h of culture. Moreover, IL-6 appeared involved in the up-regulation of TGF-beta 1, because the addition of a neutralizing anti-IL-6 antibody to Tat-treated PB monocyte cultures significantly reduced the amounts of TGF-beta 1 recovered in the culture supernatants after 96 h. The present demonstration that HIV-1 Tat protein directly up-regulates IL-6 expression and stimulates TGF-beta 1 production both directly and indirectly, through early IL-6 production, could have important implications in the pathogenesis of HIV-1 disease.
在本研究中，我们评估了1型人类免疫缺陷病毒（HIV-1）重组Tat蛋白对外周血（PB）单核细胞中两种炎性细胞因子——白细胞介素-6（IL-6）和转化生长因子-β1（TGF-β1）的mRNA表达及蛋白合成的影响。添加1微克/毫升重组Tat后，PB单核细胞培养上清液中在24 - 48小时后可检测到IL-6蛋白的最高水平，而TGF-β1则呈现出较慢且逐渐增加的趋势，仅在培养72 - 96小时后才达到最高水平。同样，对mRNA稳态水平的分析显示，培养24小时后IL-6 mRNA表达急剧增加，随后缓慢下降。另一方面，TGF-β1 mRNA表达仅在培养72 - 96小时后才缓慢增加。此外，IL-6似乎参与了TGF-β1的上调，因为在Tat处理的PB单核细胞培养物中添加中和性抗IL-6抗体，显著降低了96小时后培养上清液中回收的TGF-β1量。目前关于HIV-1 Tat蛋白直接上调IL-6表达，并通过早期IL-６的产生直接和间接刺激TGF-β1产生的证明，可能对HIV-1疾病的发病机制具有重要意义。
