Effects of megakaryocyte growth and development factor (thrombopoietin) on liver endothelial cells in vitro

Thrombopoietin (TPO) is the major regulator of growth and differentiation of megakaryocytes. Recent studies have shown that TPO also has activity on hematopoietic lineages other than megakaryocytes. However, little is known about the effects of TPO on nonhematopoietic cells expressing the TPO receptor, such as endothelial cells (EC). We have previously shown that specific murine liver EC (LEC-1) located in the hepatic sinusoids coexpress TPO and its receptor, c-mpl. Likewise, we showed that TPO has a proliferative effect on LEC-1. In this study, we have further examined the effects of TPO on other biological functions of LEC-1. Stimulation with TPO induced secretion of proinflammatory cytokines (i.e., IL-1beta, IL-6, TNF-alpha) from LEC-1. TPO-induced proliferation of LEC-1 was synergistically enhanced with the addition of TNF-alpha. TPO also induced the proliferation of LEC-1 in the presence of IFN-gamma, which alone inhibited the growth of these cells. TPO has no effect on other endothelial cell functions such as nitric oxide production and adhesion molecule expression. These observations establish a novel activity of TPO on murine liver endothelial cells in terms of inducing cytokine production by these cells. Our results suggest that this cytokine may act synergistically with other cytokines to induce LEC-1 proliferation.