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

J Immunol. 2002 Oct 15;169(8):4288-97. doi: 10.4049/jimmunol.169.8.4288.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • DNA, Complementary
  • IL19 protein, human
  • Il19 protein, mouse
  • Interleukin-6
  • Interleukins
  • Reactive Oxygen Species
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Interleukin-10

Associated data

  • GENBANK/AF453945
  • GENBANK/AF453946
  • GENBANK/AF454433