Interleukin-4 suppresses inflammatory cytokine gene transcription in porcine macrophages

Inflammatory cytokines, including interleukin (IL)‐1α, IL‐1β, IL‐8, and tumor necrosis factor α (TNF‐α) are produced by macrophages in response to a variety of pathogenic stimuli. We show here that the expression of inflammatory cytokines is suppressed by IL‐4 at the transcriptional level. Interleuk...

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Bibliographic Details
Published in:Journal of leukocyte biology 1994-10, Vol.56 (4), p.507-513
Main Authors: Zhou, Yaling, Lin, Gaofeng, Baarsch, Mary Jo, Scamurra, Ronald W., Murtaugh, Michael P.
Format: Article
Language:English
Subjects:
Animals
Base Sequence
cytokines
Cytokines - genetics
gene expression
In Vitro Techniques
Inflammation - physiopathology
Interleukin-4 - pharmacology
Interleukins - physiology
interleukin‐4
Lipopolysaccharides - pharmacology
macrophage
Macrophages, Alveolar - drug effects
Molecular Sequence Data
Swine
Transcription, Genetic - drug effects
Tumor Necrosis Factor-alpha - physiology
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Summary:Inflammatory cytokines, including interleukin (IL)‐1α, IL‐1β, IL‐8, and tumor necrosis factor α (TNF‐α) are produced by macrophages in response to a variety of pathogenic stimuli. We show here that the expression of inflammatory cytokines is suppressed by IL‐4 at the transcriptional level. Interleukin‐4, when added together with bacterial lipopolysaccharide (LPS), suppressed LPS‐induced increases in mRNA levels of IL‐1α, IL‐1β, IL‐8, and TNF‐α in alveolar macrophages. The level of suppression was dependent on dose and time of exposure and reached a maximum of 75–80% of uninduced values for IL‐1α, IL‐8, and TNF. Interleukin‐1β expression was completely inhibited by IL‐4. The amount of secreted protein, as determined by TNF‐α bioassay, was also suppressed by IL‐4. Half‐maximal suppression occurred at IL‐4 concentrations between 0.02 and 0.1 ng/ml for all inflammatory cytokines. Nuclear run‐on assays showed that IL‐4 suppressed transcriptional activity of all inflammatory cytokines. Messenger RNA stability was not changed by IL‐4. The data suggest that IL‐4 plays an important transcriptional role in the regulation of alveolar macrophage inflammatory activities in respiratory disease and raise the possibility that IL‐4 may function in vivo as a coordinator of inflammatory and immune responses J. Leukoc. Biol. 56: 507–513; 1994.
ISSN:0741-5400
1938-3673
DOI:10.1002/jlb.56.4.507