IL-10 in Myeloma Cells

Abstract

In addition to interleukin (IL)-6, IL-10 is considered as one of the most important cytokines regulating the proliferation and cellular characteristics of myeloma cells. It is still unclear from the clinical data how serum IL-10 levels of various stages of myeloma, are related to clinical manifestations of this disease. Several studies have reported that IL-10 affects myeloma cells by stimulating secondary signals for cell proliferation through oncostatin M (OSM) and IL-11. In experiments using human myeloma cell lines established at our laboratory, IL-10 seemed to be expressed in half of myelomas simultaneously with OSM, and to be correlated with c-maf, a transcription factor, which has been known to be overexpressed in myelomas with t(14;16)(q32;q23). In addition, IL-10 abolishes all trans retinoic acid (ATRA)-induced growth inhibition of myeloma cells. The expression and production of IL-10 in myeloma patients may be important for sub-categorization and the establishment of a case-oriented therapy.

TPL2 kinase regulates the inflammatory milieu of the myeloma niche

“…11,14,15 The anti-inflammatory cytokine IL-10 has also been shown to provide direct growth support to myeloma cells. 16,17 Whereas IL-1b and TNF-a mainly act by activating the nuclear factor kB (NF-kB) pathway in myeloma cells, 18,19 IL-6 and IL-10 exert their complex actions through the Janus kinase/signal transducer and activator of transcription pathway as well as the mitogen-activated protein (MAP) kinase and phosphatidylinositol 3-kinase/AKT pathways. 20,21 Durie and coauthors highlighted the importance of macrophages as a potential source of paracrine inflammatory cytokines in myeloma in an early study.…”

Additive/Synergistic Effects of Interleukin-6 and Interleukin-10 on the Proliferation of Human Myeloma Cells

“…four of ten human myeloma cell lines produce IL-10 spontaneously [6,7] . Elevated IL-10 levels were detected in serum from about 50% of patients having multiple myeloma showing a relation to the clinical manifestation [8] . IL-10 exerts its biologic effects on cells by specific cell surface receptors which are composed of two distinct subunits, activating the JAK/STAT signalling pathway.…”

Nucleosomes activate NF‐κB in endothelial cells for induction of the proangiogenic cytokine IL‐8

“…24 We used RT-PCR to examine whether nucleosomes increased IL-8 mRNA, as well as other angiogenic cytokines and growth factor mRNAs known to be expressed in endothelial cells or tumor tissue, namely, IL-6, IL-10, TNF-␣, VEGF and FGF-2. [25][26][27][28][29][30] Comparison of the angiogenesis-related mRNAs with 2 housekeeping genes indicated that nucleosomes increased IL-6 and IL-8 mRNA 3-and 5-fold, respectively (Fig. 3).…”