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Cloning, expression and initial characterisation of interleukin-19 (IL-19), a novel homologue of human interleukin-10 (IL-10)

Abstract

Interleukin-10 (IL-10) is a pleiotropic cytokine with important immunoregulatory functions whose actions influence activities of many of the cell-types in the immune system. We report here identification and cloning of a gene and corresponding cDNAs encoding a novel homologue of IL-10, designated IL-19. IL-19 shares 21% amino acid identity with IL-10. The exon/intron structure of IL-19 is similar to that of the human IL-10 gene, comprising five exons and four introns within the coding region of the IL-19 cDNA. There are at least two distinct IL-19 mRNA species that differ in their 5′-sequences, suggesting the existence of an intron in the 5′-sequences of coding portion of the IL-19 gene. The longer 5′-sequence contains an alternative initiating ATG codon that is in-frame with the rest of the coding sequence. The expression of IL-19 mRNA can be induced in monocytes by LPS-treatment. The appearance of IL-19 mRNA in LPS-stimulated monocytes was slightly delayed compared to expression of IL-10 mRNA: significant levels of IL-10 mRNA were detectable at 2 h post-stimulation, whereas IL-19 mRNA was not detectable until 4 h. Treatment of monocytes with IL-4 or IL-13 did not induce de novo expression of IL-19, but these cytokines did potentiate IL-19 gene expression in LPS-stimulated monocytes. In addition, GM-CSF was capable of directly inducing IL-19 gene expression in monocytes. IL-19 does not bind or signal through the canonical IL-10 receptor complex, suggesting existence of an IL-19 specific receptor complex, the identity of which remains to be discovered.

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Correspondence to G Gallagher or SV Kotenko.

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This work was supported by the Gastric Neoplasms Fund (GG, JE, JP). JE is supported in partby the Breast Cancer Campaign. This study was supported in part by American Heart Association Grant AHA#9730247N and by State of New Jersey Commissionon Cancer Research Grant #799–021 to SVK, and by United States Public Health Services Grants RO1-CA46465 and 1P30-CA72720 from the National Cancer Institute, RO1 AI36450 and RO1 AI43369 from the National Institute of Allergy and Infectious Diseases and an award from the Milstein Family Foundation to SP.

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Gallagher, G., Dickensheets, H., Eskdale, J. et al. Cloning, expression and initial characterisation of interleukin-19 (IL-19), a novel homologue of human interleukin-10 (IL-10). Genes Immun 1, 442–450 (2000). https://doi.org/10.1038/sj.gene.6363714

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