Human T-Cell Leukemia Virus Type I Tax Protein Induces the Expression of IL-6R and soluble IL-6R production

2001 Fiscal Year Final Research Report Summary

• Project/Area Number: 12670275
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Virology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: HORIUCHI Sankichi Department of Microbiology and Molecular Virology, Tokyo Medical and Dental University, Lecturer, 大学院・医歯学総合研究科, 講師 (60014081)
• Project Period (FY): 2000 – 2001
• Keywords: HTLV-1 / IL-6R / Soluble IL-6R / ATL / HAM / IL-6 / Jak / STAT

Research Abstract

Aim : The soluble interleukin 6 receptor (sIL-6R) circulates at elevated levels in HTLV-I infected patients compared with the healthy person. To elucidate the cause of this high level release of SIL-6R in HTLV-I infected patients, we investigated expression of the IL-6R or sIL-6R in T-cells infected with HTLV-I. Results and DiscussionrThrough our examination, it was found that although some HTLV-I-non infected cell lines expressed IL-6R, all HTLV-I-infected cell lines tested expressed IL-6R.
Results and Discussion : Through our examination, it was found that although some HTLV-I-non-infected cell lines expressed IL-6R, all HTLV-I-infected cell lines tested expressed IL-6R, Although the TY8-3 T-cell established from a thymoma did not express IL-6R, the HTLV-I infected isogenic cell lines, TY8-3/MT-2 and TY8-3/TCL-Kan expressed IL-6R. The release of proteolytically cleaved (PC)-sIL-6R was demonstrated on MT-2, MT-4, TY8-3/MT-2 and TY8 3/TCL-Kan, but not HTLV-I negative parental TY8-3 by ELISA. Induction of the Tax in JPX-9 cells by CdCl_2 results in the expression of not only IL-6R but also release of the PC-IL-6R, but not in JPX-9/M. Our results demonstrate that expression of the IL-6R and release of the PC-'sIL 6R are induced by HTLV-I or Tax. Hence, it may contribute to affected tissues, in HTLV-I associated inflammatory diseases, because the presence of sIL-6R is central to the regulation of IL-6-mediated responses in signaling for inflammatory cytokine IL-6 in the cells which are not expressed the cognate IL-6R.