Cloning, expression and initial characterization of interleukin-19 (IL-19), a novel homologue of human interleukin-10 (IL-10).
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.
Gallagher
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University of Glasgow Department of Surgery, Queen Elizabeth Building, Glasgow Royal Infirmary, 10 Alexandra Parade, Glasgow G312ER, Scotland, UK. Grant@laboratory.gg
Dickensheets
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Eskdale
J
J
Izotova
L S
LS
Mirochnitchenko
O V
OV
Peat
J D
JD
Vazquez
N
N
Pestka
S
S
Donnelly
R P
RP
Kotenko
S V
SV
D020121:5' Untranslated Regions; D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D007378:Interleukins; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D020121:5' Untranslated Regions; D017931:DNA Primers; D018076:DNA, Complementary; C421250:IL19 protein, human; D007378:Interleukins; D012333:RNA, Messenger; D016753:Interleukin-10