Diminished responses to IL-13 by human monocytes differentiated in vitro: role of the IL-13Ralpha1 chain and STAT6.
The primary IL-13 receptor complex on human monocytes is believed to be a heterodimer comprised of the IL-4R alpha chain and the IL-2R gamma chain (gamma(c))-like molecule, IL-13R alpha1. mRNA levels for IL-13R alpha1, but not IL-4R alpha, were markedly decreased in in vitro monocyte-derived macrophages (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 express gamma(c) and IL-13R alpha1 showed that IL-13 can activate STAT6 in IL-13R alpha1-positive THP-1 cells but not in gamma(c)-positive, IL-13R alpha1-negative Daudi cells. IL-13 activation of STAT6 was reduced in MDMac which was associated with diminished IL-13-induced expression of CD23 and MHC class II. However, with reduced IL-13R alpha1 expression and low nuclear STAT6 activity, some IL-13-induced responses were unaltered in magnitude in MDMac. In the absence of functional IL-13R alpha1 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 essential component of the IL-13 receptor complex on MDMac.
Hart
P H
PH
Department of Microbiology and Infectious Diseases, School of Medicine, Flinders University of South Australia, Adelaide, Australia. prue.hart@flinders.edu.au
Bonder
C S
CS
Balogh
J
J
Dickensheets
H L
HL
Vazquez
N
N
Davies
K V
KV
Finlay-Jones
J J
JJ
Donnelly
R P
RP
D001483:Base Sequence; D002454:Cell Differentiation; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis; D018793:Interleukin-13 / Q000378:metabolism / Q000494:pharmacology*; D053661:Interleukin-13 Receptor alpha1 Subunit; D015847:Interleukin-4 / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017455:Receptors, IgE / Q000096:biosynthesis; D018123:Receptors, Interleukin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D050800:STAT6 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D017931:DNA Primers; D000949:Histocompatibility Antigens Class II; C508181:IL13RA1 protein, human; D007375:Interleukin-1; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D012333:RNA, Messenger; D017455:Receptors, IgE; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4