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  • Cytokine-dependent but acquired immunity-independent arthritis caused by DNA escaped from degradation.

Cytokine-dependent but acquired immunity-independent arthritis caused by DNA escaped from degradation.

Proceedings of the National Academy of Sciences of the United States of America (2010-10-27)
Kohki Kawane, Hiromi Tanaka, Yusuke Kitahara, Shin Shimaoka, Shigekazu Nagata
ABSTRACT

DNase II digests the chromosomal DNA in macrophages after apoptotic cells and nuclei from erythroid precursors are engulfed. The DNase II-null mice develop a polyarthritis that resembles rheumatoid arthritis. Here, we showed that when bone marrow cells from the DNase II-deficient mice were transferred to the wild-type mice, they developed arthritis. A deficiency of Rag2 or a lack of lymphocytes accelerated arthritis of the DNase II-null mice, suggesting that the DNase II(-/-) macrophages were responsible for triggering arthritis, and their lymphocytes worked protectively. A high level of TNFα, IL-1β, and IL-6 was found in the affected joints of the DNase II-null mice, suggesting an inflammatory-skewed cytokine storm was established in the joints. A lack of TNFα, IL-1β, or IL-6 gene blocked the expression of the other cytokine genes as well and inhibited the development of arthritis. Neutralization of TNFα, IL-1β, or IL-6 had a therapeutic effect on the developed arthritis of the DNase II-null mice, indicating that the cytokine storm was essential for the maintenance of arthritis in the DNase II-deficient mice. Methotrexate, an antimetabolite that is often used to treat patients with rheumatoid arthritis, had a therapeutic effect with the DNase II-null mice. These properties of arthritis in the DNase II-null mice were similar to those found in human systemic-onset juvenile idiopathic arthritis or Still's disease, indicating that the DNase II-null mice are a good animal model of this type of arthritis.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Deoxyribonuclease II from porcine spleen, Type IV, lyophilized powder, 2,000-6,000 Kunitz units/mg protein (biuret)
Sigma-Aldrich
Deoxyribonuclease II from bovine spleen, Type V, essentially salt-free, lyophilized powder, ≥1,000 units/mg protein