Cloning of a cDNA encoding bovine interleukin-18 and analysis of IL-18 expression in macrophages and its IFN-gamma-inducing activity.
Interleukin-18 (IL-18) is a recently described cytokine that enhances interferon-gamma (IFN-gamma) production, either independently or synergistically with IL-12. These properties identify IL-18 as an immunoregulatory cytokine that may be pivotal in host defense against intracellular pathogens. We have isolated and sequenced a cDNA encoding bovine IL-18. The open reading frame (ORF) is 582 bp in length, encoding a predicted 192 amino acid (aa) precursor protein. Multiple sequence alignment demonstrated that bovine IL-18 has 65% and 78% identity with the predicted amino acid sequences of murine and human IL-18, respectively. IL-18 mRNA was constitutively present in bovine peripheral blood monocyte-derived macrophages (MDM), with no upregulation on stimulation with lipopolysaccharide (LPS). IL-18 transcripts were weakly detected in B lymphocytes but inducible in the B cell line BL-3. Human recombinant IL-18 (rHuIL-18) induced IFN-gamma production by PHA-stimulated peripheral blood mononuclear cells (PBMC), which was potentiated by rHuIL-12. Further, rHuIL-12 and rHuIL-18 enhanced proliferation of untreated PBMC. Antigen-specific T cell lines demonstrated IL-18-dependent enhancement of IFN-gamma production, indicating that bovine T cells are one of the leukocyte subsets that respond to IL-18. Analysis of IL-18 expression and its ability to induce IFN-gamma production by bovine lymphocytes are important considerations for understanding mechanisms of protective immunity and designing vaccines for intracellular pathogens.
Shoda
L K
LK
Department of Veterinary Microbiology and Pathology, Washington State University, Pullman 99164-7040, USA.
Zarlenga
D S
DS
Hirano
A
A
Brown
W C
WC
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002417:Cattle; D002478:Cells, Cultured; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics*; D005786:Gene Expression Regulation / Q000502:physiology*; D005815:Genetic Code; D006801:Humans; D007369:Interferon Inducers; D007371:Interferon-gamma / Q000096:biosynthesis*; D020382:Interleukin-18 / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D016176:T-Lymphocyte Subsets / Q000378:metabolism
D018076:DNA, Complementary; D007369:Interferon Inducers; D020382:Interleukin-18; D007371:Interferon-gamma