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

• Published in: International journal of cancer 2006-08, Vol.119 (4), p.823-830
• Main Authors: Horiuchi, Sankichi, Yamamoto, Norio, Dewan, Md. Zahidunnabi, Takahashi, Yoshiaki, Yamashita, Atsuya, Yoshida, Tsutomu, Nowell, Mari A., Richards, Peter J., Jones, Simon A., Yamamoto, Naoki
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Cell Line; Cell Proliferation; Culture Media; Gene Expression Regulation; Gene Products, tax - metabolism; HTLV‐I; Human T-lymphotropic virus 1; Human T-lymphotropic virus 1 - physiology; Human viral diseases; Humans; IL‐6R; Infectious diseases; Interleukin-6 - pharmacology; Medical sciences; Receptors, Interleukin-6 - genetics; Receptors, Interleukin-6 - metabolism; Signal Transduction; Solubility; STAT3; STAT3 Transcription Factor - metabolism; Tumors; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.21918

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. © 2006 Wiley‐Liss, Inc.