Human T-cell leukemia virus type-I tax induces expression of interleukin-6 receptor (IL-6R): Shedding of soluble IL-6R and activation of STAT3 signaling
Human T-cell leukemia virus type-I tax induces expression of interleukin-6 receptor (IL-6R): Shedding of soluble IL-6R and activation of STAT3 signaling
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DOI：
10.1002/ijc.21918
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发表时间：
2006-08-15
影响因子：
6.4
通讯作者：
Yamamoto, Naoki
中科院分区：
文献类型：
--
作者：
Horiuchi, Sankichi;Yamamoto, Norio;Yamamoto, Naoki
人类T细胞白血病病毒I型（HTLV-I）编码病毒蛋白Tax，已知其显著破坏T细胞中细胞因子、细胞因子受体和其他免疫调节蛋白的转录控制。这些因子的特定失调可以改变感染的过程和发病机制。可溶性白细胞介素-6受体（sIL-6 R）在HTLV-I感染的患者中以升高的水平循环，HTLV-I感染的T细胞的IL-6 R和sIL-6 R的高表达在临床和实验上与Tax活性相关。为了研究Tax在IL-6 R基因表达中的作用，使用JPX-9细胞系，其来源于表达Tax cDNA的Jurkat细胞系。过表达Tax可增强IL-6 R的表达，但在Tax突变型JPX-9/M细胞系中不增强。使用从HTLV-I感染患者获得的血清通过ELISA进一步证明这些观察结果的临床相关性。结果表明，HAM/TSP患者细胞内表达Tax的sIL-6 R水平明显升高，而ATL患者细胞内几乎不表达Tax。IL-6/sIL-6 R刺激HTLV-1感染的T细胞系显示gp 130介导的STAT 3活性。IL-6/sIL-6 R增强HTLV-I感染的T细胞的增殖与STAT 3的活化相关。因此，在HTLV-I相关疾病中观察到的Tax介导的IL-6 R和sIL-6 R调节可能通过激活诱导型STAT 3促进HTLV-I感染的T细胞增殖，并最终影响HTLV-I引起的T细胞恶性生长和转化。(c)2006威利-利斯公司
Human T-cell leukemia virus type-I (HTLV-I) encodes for the viral protein Tax, which is known to significantly disrupt transcriptional control of cytokines, cytokine receptors and other immuno-modulatory proteins in T cells. Specific dysregulation of these factors can alter the course and pathogenesis of infection. Soluble interleukin-6 receptor (sIL-6R) was shown to circulate at elevated levels in HTLV-I-infected patients, and high expressions of IL-6R and sIL-6R by HTLV-I-infected T cells were clinically and experimentally associated with Tax activity. To examine roles of Tax in expression of the IL-6R gene, the JPX-9 cell line was used, which is derived from Jurkat cell line expressing Tax cDNA. Over-expression of Tax enhanced IL-6R expression but not in Tax mutant JPX-9/M cell line. The clinical relevance of these observations was further demonstrated by ELISA using sera obtained from HTLV-I-infected patients. Our results revealed that sIL-6R levels were apparently elevated in HAM/TSP patients who were expressing Tax in their cells, while ATL patients' cells barely expressed Tax. HTLV-I-infected T-cell lines stimulated by IL-6/sIL-6R showed gp130-mediated STAT3 activity. IL-6/sIL-6R enhanced proliferation of HTLV-I-infected T cells in association with activation of STAT3. Consequently, Tax-mediated regulations of IL-6R and sIL-6R observed in HTLV-I-associated disorders may contribute to proliferation of HTLV-I-infected T cells through activation of inducible STAT3, and ultimately affect malignant growth and transformation of T cells by HTLV-I. (c) 2006 Wiley-Liss, Inc.