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More MS news articles for October 2002

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
Liao YC, Liang WG, Chen FW, Hsu JH, Yang JJ, Chang MS.
Graduate Institute of Biochemistry, Medical College, National Cheng Kung University, Tainan, Taiwan. Chi-Mei Medical Center, Tainan, Taiwan.

IL-10 is an immunosuppressive cytokine in the immune system.

It was in clinical trail 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.