Biochemical and Biophysical Research Communications, Vol.375, No.1, 95-100, 2008
Opposite effects of PU.1 on mast cell stimulation
An Ets-family transcription factor PU.1 is involved in the development and specific gene regulation of hematopoietic cells. PU.1 also determines the commitment between several lineages via its expression level. Although enforced expression of PU.1 in mast cells (MC) induced expression of monocyte-specific markers and morphological change from MC to monocytes. especially dendritic cells (DC), in the previous report, intracellular events Caused by PU.1 are largely unknown. In the present study, effect of PU.1 on IgE- and LPS-mediated stimulation degrees was analyzed. The amounts of IL-6, IL-13, and TNF-alpha produced from LPS-stimulated MC were markedly increased by overexpression of PU.1. In contrast, IL-6 and IL-13 production levels in response to IgE were reduced by PU.1, whereas that of TNF-alpha. was up-regulated. beta-Hexosaminidase release as a means of degranulation was decreased in PU.1 transfectants. When eicosanoid generation in response to IgE-stimulation was analyzed, overexpression of PU.1 reduced leukotriene C-4 (LTC4) release, but enhanced PGD(2) production. Microarray analysis suggested that expression of Fc epsilon R1 signal pathway related molecules were suppressed in PU.1 overexpressing MC as well as DC. These observations indicate that up-regulation of PU.1 suppresses expression of Fc epsilon R1 signal transduction-related intracellular molecules, but increases the potential of transcription activity of monocyte characters. (C) 2008 Elsevier Inc. All rights reserved.