Autocrine Production of Interleukin-6: A Mechanism of Interleukin-6 Independence in Dexamethasone-Resistant 7TD1 Murine Myeloma Cells — Oak Academic Publishing
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Autocrine Production of Interleukin-6: A Mechanism of Interleukin-6 Independence in Dexamethasone-Resistant 7TD1 Murine Myeloma Cells
Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, The ISU Biomedical Research Institute, Division of Health Sciences, Idaho State University, Pocatello, USA
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Department of Pharmaceutical Sciences, Jefferson School of Pharmacy, Thomas Jefferson University, Philadelphia, USA
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Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, The ISU Biomedical Research Institute, Division of Health Sciences, Idaho State University, Pocatello, USA
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Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, The ISU Biomedical Research Institute, Division of Health Sciences, Idaho State University, Pocatello, USA
1 Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, The ISU Biomedical Research Institute, Division of Health Sciences, Idaho State University, Pocatello, USA
2 Department of Pharmaceutical Sciences, Jefferson School of Pharmacy, Thomas Jefferson University, Philadelphia, USA
3 Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, The ISU Biomedical Research Institute, Division of Health Sciences, Idaho State University, Pocatello, USA
4 Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, The ISU Biomedical Research Institute, Division of Health Sciences, Idaho State University, Pocatello, USA
Several factors could contribute to proliferation of multiple myeloma (MM) cells independent of interleukin-6 (IL6) in the later stages of the disease. Our previous studies established a dexamethasone-resistant 7TD1 cell line (7TD1-Dxm) and have shown that one mechanism of resistance to dexamethasone is due to inhibition of cytochrome c release. We have also observed that 7TD1-Dxm cells proliferate independently of externally-added IL6. This study therefore aimed to elucidate the mechanisms responsible for IL6-independent proliferation in 7TD1-Dxm cells. Our results indicated that 7TD1-Dxm cells produced IL6 in an autocrine fashion. We have observed that dexamethasone-resistant 7TD1 cells become dexamethasone-resistant and IL6-independent for proliferation concomitantly. This strongly suggests that production of IL6 by 7TD1-Dxm cells may play an important role in the development of dexamethasone resistance. Consequently, further investigation of the molecular mechanisms responsible for IL6 production may be helpful in delineating the mechanisms leading to dexamethasone resistance.
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