Interleukin 13 Inhibits Macrophage Inflammatory Protein-1α Production from Human Alveolar Macrophages and Monocytes

Neville Berkman, Matthias John, Goedele Roesems, Peter Jose, Peter J. Barnes, K. Fan Chung*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

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 1α (MIP-1α) 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-1β-induced MIP-1α mRNA and protein expression from peripheral blood monocytes (PBM) and alveolar macrophages (AM). In PBM, basal MIP-1α protein was 20 ± 7 pM and increased following LPS and IL-1β 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-1β-induced MIP-1α mRNA expression was reduced by 43 ± 5% (P < 0.01) and 41 ± 4% (NS). In AM, IL-13 reduced LPS-induced MIP-1α protein release of 2,030 ± 242 pM by 32 ± 8% (P < 0.05) and MIP-1α mRNA by 27 ± 1% (NS). For both PBM and AM, the inhibitory effect of IL-13 on MIP-1α 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-1α from monocytes and macrophages, and as is the case with IL-4 and IL-10, may be an important mediator for suppressing inflammatory responses.

Original languageAmerican English
Pages (from-to)382-389
Number of pages8
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume15
Issue number3
DOIs
StatePublished - 1996
Externally publishedYes

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