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Multiple myeloma (MM) is typically featured by the increased levels of inflammatory cytokines in the neoplastic plasma cells (PCs) producing monoclonal immunoglobulin. PCs proliferate in the bone marrow, which will lead to extensive skeletal destruction with osteolytic lesions, osteopenia, or pathologic fractures. The diagnostic biology of MM has progressed from morphology and low-sensitivity protein analysis into multiomics-based high-throughput readout, whereas therapeutics has evolved from single active agent to potential active drug combinations underlying precision medicine. Many studies have focused on the cytokine networks that control growth, progression, and dissemination of the disease. The complexity of cytokines in MM development remains to be elucidated comprehensively. Apart from knowing that interleukin (IL)-6 is important in the pathogenesis of MM, it has been shown that IL-6 is a paracrine factor supplied by the microenvironment comprising of those cells from the myeloid compartment. Due to IL-10 was considered an immunosuppressive cytokine to promote cancer escape from immune surveillance, the role of IL-10 in this regard has been underestimated although recent advances have reported that IL-10 induces both PC proliferation and angiogenesis in MM. In addition, cumulative studies have suggested that IL-10 plays an important role in the induction of chemoresistance in many cancers; a virtual requirement of autocrine IL-10 for MM cells to escape from an IL-6-dependent proliferation loop was implicated. In this review, we summarize the available information to elucidate a new understanding of the molecular and functional roles of IL-10 in MM. [ABSTRACT FROM AUTHOR]

Objective: Human interleukin-10 (IL-10) is a dimeric and pleiotropic cytokine that plays a crucial role in cellular immunoregulatory responses. As IL-10 binds to its receptors, IL-10Ra and IL-10Rb, it will suppress or induce the downstream cellular immune responses to protect from diseases. Materials and Methods: In this study, a potential peptide derived from IL-10 based on molecular docking and structural analysis was designed and validated by a series of cell assays to block IL-10 binding to receptor IL-10Ra for the inhibition of cell growth. Results: The simulation results indicate that the designed peptide IL10NM25 bound to receptor IL-10Ra is dominated by electrostatic interactions, whereas van der Waals (VDW) and hydrophobic interactions are minor. The cell experiments showed that IL10NM25 specifically binds to receptor IL-10Ra on the cell surface of two B-lineage cell lines, B lymphoma derived (BJAB), and lymphoblastoid cell line, whereas the mutant and scramble peptides are not able to suppress the binding of IL-10 to receptor IL-10Ra, consistent with the molecular simulation predictions. Conclusion: This study demonstrates that structure-based peptide design can be effective in the development of peptide drug discovery. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is typically featured by the increased levels of inflammatory cytokines in the neoplastic plasma cells (PCs) producing monoclonal immunoglobulin. PCs proliferate in the bone marrow, which will lead to extensive skeletal destruction with osteolytic lesions, osteopenia, or pathologic fractures. The diagnostic biology of MM has progressed from morphology and low-sensitivity protein analysis into multiomics-based high-throughput readout, whereas therapeutics has evolved from single active agent to potential active drug combinations underlying precision medicine. Many studies have focused on the cytokine networks that control growth, progression, and dissemination of the disease. The complexity of cytokines in MM development remains to be elucidated comprehensively. Apart from knowing that interleukin (IL)-6 is important in the pathogenesis of MM, it has been shown that IL-6 is a paracrine factor supplied by the microenvironment comprising of those cells from the myeloid compartment. Due to IL-10 was considered an immunosuppressive cytokine to promote cancer escape from immune surveillance, the role of IL-10 in this regard has been underestimated although recent advances have reported that IL-10 induces both PC proliferation and angiogenesis in MM. In addition, cumulative studies have suggested that IL-10 plays an important role in the induction of chemoresistance in many cancers; a virtual requirement of autocrine IL-10 for MM cells to escape from an IL-6-dependent proliferation loop was implicated. In this review, we summarize the available information to elucidate a new understanding of the molecular and functional roles of IL-10 in MM., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Tzu Chi Medical Journal.)