Cytokine production by a megakaryocytic cell line

Abstract

The regulation of megakaryopoeisis by cytokines is not yet well understood. It is possible that autocrine loops are established during megakaryocyte growth and differentiation, aiding in the maturation of these cells. The CHRF-288-11 human megakaryoblastic cell line has been examined for cytokine production in growing cells and cells stimulated to differentiate by the addition of phorbol esters. It has been demonstrated that these cells produce RNA corresponding to the interleukins IL-1 alpha, 1 beta, 3, 7, 8, and 11, granulocyte-macrophage colony stimulating factor (GM-CSF), stem cell factor (SCF), transforming growth factor-beta (TGF-beta), tumor necrosis factor-alpha (TNF-alpha), interferon-alpha (INF-alpha), and basic fibroblast growth factor (bFGF). Additionally, RNA corresponding to the receptors for IL-6, GM-CSF, SCF, INF-alpha, beta, bFGF, and monocyte colony stimulating factor (M-CSF) were also expressed by the cells. The receptor for TNF-alpha was detected immunologically. Analysis at the protein level demonstrated that significant amounts of INF-alpha, TNF-alpha, GM-CSF, SCF, IL-1 alpha, and a soluble form of the IL-6 receptor were produced by the cells. Addition of phorbol esters to CHRF-288-11 cells enhances their megakaryocytic phenotype; such treatment also results in increased secretion of INF-alpha, TNF-alpha, and GM-CSF. These results suggest that potential autocrine loops are established during the differentiation of CHRF-288-11 cells, which may alter the capability of the cell to differentiate. These findings are similar to those recently obtained for marrow-derived megakaryocytes (Jiang et al.) suggesting that CHRF-288-11 cells provide a useful model system for the study of cytokine release during megakaryocyte differentiation.

Expression of interleukin (IL) 1 type I and type II receptors in megakaryocytic cells and enhancing effects of IL‐1β on megakaryocytopoiesis and NF‐E2 expression

“…The present study is the first report on the identification of IL‐1 RI and RII receptors on the megakaryocytic lineage. The findings that all the four megakaryocytic cell lines and cultured cord blood megakaryocytic cells expressed IL‐1β mRNA are in agreement with those reported in human bone marrow megakaryocytes (Jiang et al , 1994), megakaryocytic cell lines HU3, MBO2 (Sandrock et al , 1996) and CHRF (Soslau et al , 1997). IL‐1β might exert its effects on the megakaryocytic lineage via an autocrine or paracrine activity.…”

Platelet expression of tumour necrosis factor-alpha (TNF-α), TNF receptors and intercellular adhesion molecule-1 (ICAM-1) in patients with proliferative diabetic retinopathy

“…The significance of TNF-a binding to platelets lies in that this cytokine induces thrombocyte processes known to contribute to the microvascular pathology observed in PDR, such as platelet aggregation and adhesion to endothelium [3,4], and production of vasoactive agents, such as nitric oxide, free radicals and prostacyclin [24]. Since platelets and megakaryocytes are known to secrete TNF-a [6,7,25], platelet staining for this cytokine may be due to its cytoplasmic presence. However, the findings that platelet staining for TNF-a directly correlates with the expression of TNF-RI and TNF-RII may also indicate that TNF-a detected on the platelet surface may be bound to its receptors.…”

Megakaryocytes as immune cells

“…IL‐1α/β released by platelets activates immune cells, endothelial cells, and synovial fibroblasts and has been implicated in the pathogenesis of RA and SLE . The presence of IL‐1α and IL‐1β at a protein and mRNA level has been documented in murine MKs, with some supportive data from human MK cell lines and primary MKs . MK‐conditioned media activates synovial fibroblasts in an IL‐1R‐dependent manner, whereas engraftment of WT but not IL‐1α/β‐deficient MKs restores arthritis susceptibility in mice resistant to arthritis.…”