Inflammatory cytokines and the reactivation of Kaposi's sarcoma-associated herpesvirus lyric replication
Inflammatory cytokines and the reactivation of Kaposi's sarcoma-associated herpesvirus lyric replication
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DOI：
10.1006/viro.1999.0077
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发表时间：
2000-01-05
期刊：
影响因子：
3.7
通讯作者：
Ganem, D
中科院分区：
文献类型：
--
作者：
Chang, J;Renne, R;Ganem, D
卡波西肉瘤是一种复杂的增生性病变，长期以来一直被怀疑依赖于外源性旁分泌信号分子来刺激其增殖、血管生成和炎症成分。特别是，临床和实验观察都指出了炎症细胞因子作为KS发展的容许因子的潜在作用，但KS发病机制也严重依赖于外源性疱疹病毒（KS相关疱疹病毒（KSHV））的感染。为了研究炎性细胞因子和KSHV复制之间可能的联系，我们测试了这些细胞因子在潜伏感染的BCBL-1细胞系中诱导裂解病毒再活化的能力。干扰素-γ持续激活KSHV复制，而肿瘤坏死因子、白细胞介素-1、白细胞介素-2、白细胞介素-6、粒细胞-巨噬细胞集落刺激因子和碱性成纤维细胞生长因子则不激活。糖皮质激素也未能诱导裂解KSHV在这些细胞中的生长，但：离子霉素，钙离子载体，诱导复制和强烈增强已知的佛波醇酯的诱导作用。干扰素-α对离子霉素诱导的KSHV具有剂量依赖性抑制作用。干扰素-γ作为KSHV体外诱导的激活剂和干扰素-α作为KSHV体外诱导的抑制剂的鉴定与体内观察良好相关，并首次证明炎性细胞因子可以直接调节KSHV复制。(C)北京大学出版社.
Kaposi's sarcoma (KS) is a complex proliferative lesion long suspected of being dependent on exogenous paracrine signaling molecules to stimulate its proliferative, angiogenic, and inflammatory components. In particular, both clinical and experimental observations have pointed to a potential role for inflammatory cytokines as permissive factors for KS development, but KS pathogenesis is also critically dependent on infection by an exogenous herpesvirus, the KS-associated herpesvirus (KSHV). To examine the possible links between inflammatory cytokines and KSHV replication, we tested for the ability of such cytokines to induce lytic viral reactivation in the latently infected BCBL-1 cell line. lnterferon-gamma consistently activated KSHV replication, whereas tumor necrosis factor, interleukin-1, interleukin-2, interleukin-6, granulocyte-macrophage colony stimulating factor, and basic fibroblast growth factor did not. Glucocorticoids also failed to induce lytic KSHV growth in these cells, bur: ionomycin, a calcium ionophore, induced replication and strongly augmented the known inductive effects of phorbol esters. Interferon-alpha had a dose-dependent inhibitory effect on KSHV induction by ionomycin. The identification of interferon-gamma as an activator and interferon-alpha as an inhibitor of KSHV induction in vitro correlates well with in vivo observations and demonstrates for the first time that inflammatory cytokines can directly modulate KSHV replication. (C) 2000 Academic Press.