Effect of IL-12 Encoding Plasmid Administration on Tight-Skin Mouse

• Published in: Biochemical and biophysical research communications 2001-01, Vol.280 (3), p.707-712
• Main Authors: Tsuji-Yamada, Junko, Nakazawa, Masatoshi, Takahashi, Kazuo, Iijima, Katsumasa, Hattori, Shunji, Okuda, Kenji, Minami, Mutsuhiko, Ikezawa, Zenro, Sasaki, Tetsuo
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Antinuclear - blood; antinuclear antibody; collagen; gene therapy; Genetic Therapy; IL-12; IL-4; Injections, Intramuscular; Interferon-gamma - blood; Interleukin-12 - blood; Interleukin-12 - genetics; Interleukin-12 - therapeutic use; Interleukin-4 - blood; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; plasmid; Plasmids - administration & dosage; Plasmids - genetics; Scleroderma, Systemic - genetics; Scleroderma, Systemic - immunology; Scleroderma, Systemic - pathology; Scleroderma, Systemic - therapy; skin; Skin - pathology; systemic sclerosis; Th1 Cells - immunology; Th1/Th2; Th2 Cells - immunology; tight-skin mouse
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.2000.4171

The tight-skin (Tsk/+) mutant mice, a putative murine model of scleroderma, are characterized by the excessive deposition of collagen and the presence of antinuclear antibodies. Type 2 cytokines, such as IL-4 and IL-6, are capable of regulating the synthesis of various matrix molecules, including type I collagen, by fibroblasts. IL-12 is well known to induce type 1 cytokine production and to reduce type 2 activity. Here, we examined the effect of IL-12 encoding plasmid (pCAGGSIL-12) on the disease progression of Tsk/+ mice. pCAGGSIL-12 plasmid or pCAGGS parental vector was injected intramuscularly 7 times at 3 week intervals into Tsk/+ mice. One week after the last injection, pCAGGSIL-12 administered Tsk/+ mice exhibited a marked decrease in the skin thickness compared with the mice treated with pCAGGS vector. The serum levels of antinuclear antibodies were diminished in pCAGGSIL-12 treated mice. IL-4 production by spleen cells from pCAGGSIL-12 plasmid treated mice was significantly lower than that from vector treated mice. These results indicate that pCAGGSIL-12 administration into Tsk/+ mice had beneficial effects in preventing the collagen accumulation in the skin and suppressing the autoimmunity via improvement of Th1/Th2 balance. The present study suggests that the IL-12 encoding plasmid administration might have a therapeutic effect on systemic sclerosis.