Interleukin-4 suppresses inflammatory cytokine gene transcription in porcine macrophages.
Inflammatory cytokines, including interleukin (IL)-1 alpha, IL-1 beta, IL-8, and tumor necrosis factor alpha (TNF-alpha) 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-1 alpha, IL-1 beta, IL-8, and TNF-alpha 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-1 alpha, IL-8, and TNF. Interleukin-1 beta expression was completely inhibited by IL-4. The amount of secreted protein, as determined by TNF-alpha 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.
Zhou
Y
Y
Department of Veterinary PathoBiology, College of Veterinary Medicine, University of Minnesota, St. Paul.
Lin
G
G
Baarsch
M J
MJ
Scamurra
R W
RW
Murtaugh
M P
MP
D000818:Animals; D001483:Base Sequence; D016207:Cytokines / Q000235:genetics*; D066298:In Vitro Techniques; D007249:Inflammation / Q000503:physiopathology; D015847:Interleukin-4 / Q000494:pharmacology*; D007378:Interleukins / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000187:drug effects*; D008969:Molecular Sequence Data; D013552:Swine; D014158:Transcription, Genetic / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D016207:Cytokines; D007378:Interleukins; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4