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カワネ コウキ
KAWANE KOKI
川根 公樹 所属 京都産業大学 生命科学部 先端生命科学科 職種 准教授 |
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| 言語種別 | 英語 |
| 発行・発表の年月 | 2010/11 |
| 形態種別 | その他 |
| 標題 | Cytokine-dependent but acquired immunity-independent arthritis caused by DNA escaped from degradation |
| 執筆形態 | その他 |
| 掲載誌名 | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA |
| 出版社・発行元 | NATL ACAD SCIENCES |
| 巻・号・頁 | 107(45),pp.19432-19437 |
| 著者・共著者 | Kohki Kawane, Hiromi Tanaka, Yusuke Kitahara, Shin Shimaoka, Shigekazu Nagata |
| 概要 | 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 wildtype 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 TNF alpha, IL-1 beta, 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 TNF alpha, IL-1 beta, or IL-6 gene blocked the expression of the other cytokine genes as well and inhibited the development of arthritis. Neutralization of TNF alpha, IL-1 beta, 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. |
| DOI | 10.1073/pnas.1010603107 |
| ISSN | 0027-8424 |