IL-19 induces production of IL-6 and TNF-alpha and results in cell apoptosis through TNF-alpha.
IL-10 is an immunosuppressive cytokine in the immune system. It was in clinical trial as an anti-inflammatory therapy for inflammatory bowel disease and various autoimmune diseases such as psoriasis, rheumatoid arthritis, and multiple sclerosis. IL-19 belongs to the IL-10 family, which includes IL-10, IL-19, IL-20, IL-22, melanoma differentiation-associated gene (MDA-7, IL-24), and AK155 (IL-26). Despite a partial homology in their amino acid sequences, they are dissimilar in their biologic functions. Little is known about the biologic function and gene regulation of IL-19. To understand the gene regulation of human IL-19, we identified a human IL-19 genomic clone and analyzed its promoter region. Five fusion genes containing different regions upstream of exon 1 linked to a luciferase reporter gene were expressed in the canine kidney epithelial-like Madin-Darby canine kidney cells. A fusion gene containing 394 bp showed luciferase activity 7- to 8-fold higher than the negative control of the promoterless fusion gene. We also isolated a full-length mouse cDNA clone. Mouse IL-19 shared 71% amino acid identity with human IL-19. Treatment of monocytes with mouse IL-19 induced the production of IL-6 and TNF-alpha. It also induced mouse monocyte apoptosis and the production of reactive oxygen species. Taken together, our results indicate that mouse IL-19 may play some important roles in inflammatory responses because it up-regulates IL-6 and TNF-alpha and induces apoptosis.
Liao
Yuan-Chun
YC
Graduate Institute of Biochemistry, College of Medicine, National Cheng Kung University, Tainan, Taiwan 70.
Liang
Wei-Guang
WG
Chen
Feng-Wei
FW
Hsu
Ju-Hui
JH
Yang
Jiann-Jou
JJ
Chang
Ming-Shi
MS
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D001483:Base Sequence; D002460:Cell Line; D002478:Cells, Cultured; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000302:isolation & purification; D004285:Dogs; D005091:Exons / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D015850:Interleukin-6 / Q000096:biosynthesis*; D007378:Interleukins; D007438:Introns / Q000276:immunology; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000276:immunology; D017382:Reactive Oxygen Species / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000502:physiology
D018076:DNA, Complementary; C421250:IL19 protein, human; C498891:Il19 protein, mouse; D015850:Interleukin-6; D007378:Interleukins; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10