Characterization of IL-4 receptor components expressed on monocytes and monocyte-derived macrophages: variation associated with differential signaling by IL-4.
The anti-inflammatory effects of IL-4 on activated monocytes differ from those on monocyte-derived macrophages (MDMac). While IL-4 suppresses LPS-induced IL-1beta , IL-12, IL-10 and TNFalpha production by monocytes, IL-4 suppresses only IL-1beta and IL-12 production by MDMac. The U937 and Mono Mac 6 cell lines have similar cytokine responses to IL-4 as monocytes and MDMac, respectively. The IL-4Ralpha and IL-2Rgamma (gammac) chains are well-characterized components of the IL-4 receptor. Cross-linking studies with 125I-IL-4 revealed that for monocytes and U937 cells, the binding of IL-4 to the receptor components was approximately 1:1 for IL-4Ralpha:gammac. In contrast, for MDMac and Mono Mac 6 cells that have a relative reduction in gammac surface expression, the binding of IL-4 to IL-4Ralpha:gammac was approximately 3:1. Furthermore, IL-4 induced IL-4Ralpha chain phosphorylation more rapidly in MDMac and Mono Mac 6 cells than in monocytes and U937 cells. This study identifies a correlation between altered 125I-IL-4 cross-linking to IL-4Ralpha:gammac, IL-4-induced signaling and regulation of pro-inflammatory cytokine production by IL-4.
Bonder
C S
CS
Department of Microbiology and Infectious Diseases, School of Medicine and Flinders Medical Research Institute, Flinders University, Adelaide, South Australia, Australia.
Hart
P H
PH
Davies
K V
KV
Burkly
L C
LC
Finlay-Jones
J J
JJ
Woodcock
J M
JM
D015153:Blotting, Western; D002454:Cell Differentiation; D003432:Cross-Linking Reagents / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D019281:Dimerization; D005434:Flow Cytometry; D006031:Glycosylation; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism*; D007455:Iodine / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D010766:Phosphorylation; D011233:Precipitin Tests; D019948:Receptors, Interleukin-4 / Q000737:chemistry*; D015398:Signal Transduction; D013997:Time Factors; D014407:Tumor Cells, Cultured; D020298:U937 Cells
D003432:Cross-Linking Reagents; D016207:Cytokines; D019948:Receptors, Interleukin-4; D015847:Interleukin-4; D007455:Iodine