Interleukin 4 down-regulates the expression of CD14 in normal human monocytes.
Recombinant interleukin 4 (IL4) down-regulates the expression of CD14 on normal human monocytes, as assessed by flow cytometry, binding assays with radiolabeled anti-CD14 monoclonal antibody (mAb), and immunoprecipitation of 125I-labeled monocytes with anti-CD14 mAb. In parallel, CD23 expression on monocytes was strongly increased by IL4 stimulation, as assessed by both flow cytometry and immunoprecipitation. Down-regulation of surface CD14 was first detectable after 24-36 h of incubation with rIL4, and was almost complete after 4 days of culture. None of the other recombinant lymphokines tested (IL1, IL2, IL3, IL5, IL6, interferon-gamma, tumor necrosis factor alpha and beta, granulocyte-macrophage colony-stimulating factor) decreased CD14 expression. Metabolic labeling studies with [35S]methionine showed that both the membrane-associated and the soluble form of CD14 are decreased by IL4 stimulation. Northern blot analysis showed that incubation of monocytes with IL4 induced a marked decrease in CD14 mRNA. Nuclear run-off assays revealed that the IL4-dependent down-regulation of CD14 resulted from decreased transcription. Thus, IL4 exerts specific and opposite effects on the expression of monocytic antigens.
Division of Immunology, Children's Hospital, Boston, MA 02115.
R P
RP
Lauener
S M
SM
Goyert
R S
RS
Geha
D
D
Vercelli
D015703:Antigens, CD / Q000032:analysis*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis* / Q000235:genetics; D015536:Down-Regulation; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology; D018950:Lipopolysaccharide Receptors; D009000:Monocytes / Q000276:immunology*; D011233:Precipitin Tests; D012333:RNA, Messenger / Q000032:analysis; D011961:Receptors, Fc / Q000032:analysis; D017455:Receptors, IgE
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D015214:Antigens, Differentiation, Myelomonocytic; D006684:HLA-DR Antigens; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D012333:RNA, Messenger; D011961:Receptors, Fc; D017455:Receptors, IgE; D015847:Interleukin-4