Diminished responses to IL-13 by human monocytes differentiated in vitro: role of the IL-13R alpha 1 chain and STAT6

The primary IL-13 receptor complex on human monocytes is believed to be a h eterodimer comprised of the IL-4R alpha chain and the IL-2R gamma chain (ga mma(c))-like molecule, IL-13R alpha 1. mRNA levels for IL-13R alpha 1, but not IL-4R alpha, were markedly decreased in in vitro monocyte-derived macro phages (MDMac), and with increasing time of monocytes in culture correlated with the loss of IL-13 regulation of lipopolysaccharide-induced TNF-alpha production. Analysis of cell lines Daudi and THP-1 that differentially expr ess gamma(c) and IL-13R alpha 1 showed that IL-13 can activate STAT6 in IL- 13R alpha 1-positive THP-1 cells but not in gamma(c)-positive, IL-13R alpha 1-negative Daudi cells. IL-13 activation of STAT6 was reduced in MDMac whi ch was associated with diminished IL-13-induced expression of CD23 and MHC class II. However, with reduced IL-13R alpha 1 expression and low nuclear S TAT6 activity, some IL-13-induced responses were unaltered in magnitude in MDMac. In the absence of functional IL-13R alpha 1 and gamma(c), IL-13 must signal through an alternative receptor complex on MDMac. Experiments with a blocking antibody to IL-4R alpha showed that this chain remains an essent ial component of the IL-13 receptor complex on MDMac.