Interleukin 13 inhibits macrophage inflammatory protein-1 alpha production from human alveolar macrophages and monocytes. 1996

N Berkman, and M John, and G Roesems, and P Jose, and P J Barnes, and K F Chung
Department of Thoracic Medicine, National Heart and Lung Institute, Royal Brompton Hospital, London, United Kingdom.

Interleukin 13 (IL-13) is a recently described protein secreted by activated T cells and is a potent in vitro modulator of human monocyte and B-cell functions. IL-13 shares some biologic properties as well as structural similarities with IL-4. Macrophage-inflammatory protein 1 alpha (MIP-1 alpha) is a product of activated monocytes and macrophages and an important activator of T cells, monocytes, and macrophages. We determined the effect of human recombinant IL-13 on lipopolysaccharide (LPS)- and IL-1 beta-induced MIP-1 alpha mRNA and protein expression from peripheral blood monocytes (PBM) and alveolar macrophages (AM). In PBM, basal MIP-1 alpha protein was 20 +/- 7 pM and increased following LPS and IL-1 beta to 1,520 +/- 193 (P < 0.001) and 233 +/- 50 (P < 0.003) pM. IL-13 (25 ng/ml) reduced these values by 55 +/- 10% [not significant (NS)], 43 +/- 9% (P < 0.03), and 44 +/- 15% (NS), respectively. LPS- and IL-1 beta-induced MIP-1 alpha mRNA expression was reduced by 43 +/- 5% (P < 0.01) and 41 +/- 4% (NS). In AM, IL-13 reduced LPS-induced MIP-1 alpha protein release of 2,030 +/- 242 pM by 32 +/- 8% (P < 0.05) and MIP-1 alpha mRNA by 27 +/- 1% (NS). For both PBM and AM, the inhibitory effect of IL-13 on MIP-1 alpha protein was maximal at 24 h, was dose dependent with a maximal effect at 100 ng/ml, and was similar to, although slightly less potent than, that seen with IL-4. In PBM, the inhibitory effect of IL-13 required de novo protein synthesis and was not due to enhanced mRNA decay. Thus, IL-13 has inhibitory effects on the transcription of MIP-1 alpha from monocytes and macrophages, and as is the case with IL-4 and IL-10, may be an important mediator for suppressing inflammatory responses.

UI MeSH Term Description Entries
D008070 Lipopolysaccharides Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed) Lipopolysaccharide,Lipoglycans
D009000 Monocytes Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. Monocyte
D011500 Protein Synthesis Inhibitors Compounds which inhibit the synthesis of proteins. They are usually ANTI-BACTERIAL AGENTS or toxins. Mechanism of the action of inhibition includes the interruption of peptide-chain elongation, the blocking the A site of ribosomes, the misreading of the genetic code or the prevention of the attachment of oligosaccharide side chains to glycoproteins. Protein Synthesis Antagonist,Protein Synthesis Antagonists,Protein Synthesis Inhibitor,Antagonist, Protein Synthesis,Antagonists, Protein Synthesis,Inhibitor, Protein Synthesis,Inhibitors, Protein Synthesis,Synthesis Antagonist, Protein,Synthesis Inhibitor, Protein
D011506 Proteins Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein. Gene Products, Protein,Gene Proteins,Protein,Protein Gene Products,Proteins, Gene
D003513 Cycloheximide Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis. Actidione,Cicloheximide
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D006131 Growth Inhibitors Endogenous or exogenous substances which inhibit the normal growth of human and animal cells or micro-organisms, as distinguished from those affecting plant growth ( Cell Growth Inhibitor,Cell Growth Inhibitors,Growth Inhibitor,Growth Inhibitor, Cell,Growth Inhibitors, Cell,Inhibitor, Cell Growth,Inhibitor, Growth,Inhibitors, Cell Growth,Inhibitors, Growth
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D013997 Time Factors Elements of limited time intervals, contributing to particular results or situations. Time Series,Factor, Time,Time Factor

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