Induction and regulation of IL-15 expression in murine macrophages.
IL-15 is a recently described cytokine which resembles IL-2 in its biologic activities, stimulating T cell and NK cell proliferation and activation as well as enhancing B cell expansion and Ab production. Unlike IL-2, IL-15 is not produced by lymphocytes, but instead (at least among cells of the immune system) appears to be synthesized primarily by monocyte/macrophages. We have examined the induction of IL-15 in murine macrophages (by semiquantitative reverse transcriptase-PCR and bioassay) in response to a variety of different macrophage-activating stimuli and compared the regulation of IL-15 production to that of IL-12 and TNF-alpha. Optimal induction of IL-15, in each of the macrophages populations tested, was found to require both priming (IFN-gamma) and triggering (LPS, mycobacteria, or Toxoplasma gondii) stimuli. When compared with IL-12 mRNA synthesis by the same macrophages, IL-15.mRNA production was more resistant to inhibition by the down-regulatory cytokines IL-14, IL-13, and TGF-beta. Moreover, IL-10, which is inhibitory for most other monokines, increased levels of IL-15 mRNA found after stimulation. These data establish IL-15 as a product of the macrophage/monocyte lineage, which is up-regulated on activation. IL-15 could thus play an important role in the initiation of immune responses by microbial agents.
Doherty
T M
TM
Immunobiology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Seder
R A
RA
Sher
A
A
D000818:Animals; D001483:Base Sequence; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D016207:Cytokines / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics; D018664:Interleukin-12 / Q000096:biosynthesis / Q000235:genetics; D019409:Interleukin-15; D007378:Interleukins / Q000096:biosynthesis* / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects; D009163:Mycobacterium bovis / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000276:immunology; D009928:Organ Specificity; D014122:Toxoplasma / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D016207:Cytokines; D019409:Interleukin-15; D007378:Interleukins; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor