IL-19 induces production of IL-6 and TNF-alpha and results in cell apoptosis through TNF-alpha

• Published in: The Journal of immunology (1950) 2002-10, Vol.169 (8), p.4288-4297
• Main Authors: Liao, Yuan-Chun, Liang, Wei-Guang, Chen, Feng-Wei, Hsu, Ju-Hui, Yang, Jiann-Jou, Chang, Ming-Shi
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Apoptosis - immunology; Base Sequence; Cell Line; Cells, Cultured; Cloning, Molecular; DNA, Complementary - isolation & purification; Dogs; Exons - immunology; Humans; Interleukin-10 - chemistry; Interleukin-10 - genetics; Interleukin-10 - physiology; Interleukin-6 - biosynthesis; Interleukins; Introns - immunology; Male; Mice; Molecular Sequence Data; Monocytes - cytology; Monocytes - immunology; Monocytes - metabolism; Promoter Regions, Genetic - immunology; Reactive Oxygen Species - metabolism; Recombinant Proteins - biosynthesis; Recombinant Proteins - isolation & purification; Tumor Necrosis Factor-alpha - biosynthesis; Tumor Necrosis Factor-alpha - physiology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.169.8.4288

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.