Interleukin-13 (IL-13) induces IL-1 receptor antagonist gene expression and protein synthesis in peripheral blood mononuclear cells: inhibition by an IL-4 mutant protein.
Interleukin-13 (IL-13) belongs to the IL-4 gene family. Like IL-4, IL-13 induces IL-1 receptor antagonist (IL-1Ra) synthesis with no effect on IL-1beta synthesis. We investigated whether IL-13 induces IL-1Ra synthesis via a pathway similar to IL-4. In human peripheral blood mononuclear cells, IL-13 (1 to 100 ng/mL alone induced IL-1Ra synthesis in a dose-dependent manner. A single amino acid mutant form of IL-4 (hIL4.Yl24D) induced IL-1Ra synthesis, acting as a partial agonist. However, hIL-4.Yl24D inhibited IL-1Ra synthesis induced by either IL-4 or IL-13. IL-13 alone induced accumulation of IL-1Ra mRNA. Furthermore, IL-13 reduced steady- state levels for IL-1beta mRNA but enhanced those for IL-1Ra mRNA in cells stimulated with lipopolysaccharide (LPS) or IL-1alpha. Accordingly, IL-13 suppressed IL-1beta synthesis but enhanced IL-1Ra synthesis in these cells. IL-13 reduced the stability of IL-1beta mRNA (2.9 v 1.7 hours) but failed to modify the stability of IL-1Ra mRNA (2.7 v 2.5 hours). Moreover, IL-13 induced transcriptional activation of the IL-1Ra gene, but reduced IL-1beta gene transcription. Our results suggest that the commonality between IL-13 and IL-4 in inducing IL-1Ra synthesis results from the engagement of a subunit common to both receptors.
Vannier
E
E
Department of Medicine, Tufts University of Medicine, Boston, Masachusetts USA.
de Waal Malefyt
R
R
Salazar-Montes
A
A
de Vries
J E
JE
Dinarello
C A
CA
D015703:Antigens, CD / Q000737:chemistry / Q000187:drug effects; D001483:Base Sequence; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000494:pharmacology; D018793:Interleukin-13 / Q000494:pharmacology*; D053661:Interleukin-13 Receptor alpha1 Subunit; D015847:Interleukin-4 / Q000235:genetics / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008969:Molecular Sequence Data; D005810:Multigene Family; D012333:RNA, Messenger / Q000096:biosynthesis; D018123:Receptors, Interleukin / Q000737:chemistry / Q000187:drug effects; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4; D012795:Sialoglycoproteins / Q000096:biosynthesis / Q000235:genetics*; D014158:Transcription, Genetic
D015703:Antigens, CD; C508181:IL13RA1 protein, human; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4; D012795:Sialoglycoproteins; D015847:Interleukin-4