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Title: CLONING OF A CDNA ENCODING BOVINE INTERLEUKIN 18 (IL-18) AND ANALYSIS OF IL-18 EXPRESSION IN MACROPHAGES AND ITS IFN-GAMMA-INDUCING ACTIVITY

Author
item SHODA, LISL - DEPT MICRO PULLMAN, WA
item ZARLENGA, DANTE - 1265-20
item HIRANO, AYUMI - DEP VET MICRO, PULLMAN WA
item BROWN, WENDY - DEPT VET MICRO PULLMAN WA

Submitted to: Journal of Interferon and Cytokine Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/5/1999
Publication Date: N/A
Citation: N/A

Interpretive Summary: Interleukin 18 (IL-18) is an interferon gamma (IFN-gamma) inducing factor that is primarily a product of monocytes/macrophages (MF), but has also been detected in B and T lymphocytes, dendritic cells, and keratinocytes. IFN-gamma is a critical cytokine in immune responses to intracellular pathogens that activates MF to enhance MF microbial activity and T and B lymphocyte differentiation. Mounting evidence indicates that IL-18 may play a pivotal role in host defense, largely by enhancing IFN-gamma production either independently or synergistically with other cytokines. Studes suggest that IL-18, perhaps alone or in combination with other cytokines may be a promising candidate for adjuvant-based immune modulation. Because IL-18 is an important cytokine for stimulating IFN-gamma production and because of the ever increasing evidence of the role of cytokine for stimulating IFN-gamma production and the role of cytokines in protecting agriculturally important animals against disease, we cloned the bovine IL-18 cDNA and studied its transcription in leukocyte subsets as well as the activity of rhIL-18 on bovine peripheral blood mononuclear cells (PBMC) and T cell lines. Data resulting from this study will now allow us to produce this all important cytokine by recombinant DNA methods and study its role in attenuating bovine parasitic diseases.

Technical Abstract: Interleukin 18 (IL-18) is a recently described cytokine that enhances 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 is 582 bp in length, encoding a predicted 193 amino acid 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 upon 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 (rhIL-18) induced IFN-gamma production by PHA-stimulated peripheral blood mononuclear cells (PBMC), which was potentiated by rhIL-12. Further, rhIL-12 and rhIL-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.