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Role of TNFa in mice exposed to high dose radiation: its mechanisms for radioprotection
https://repo.qst.go.jp/records/69745
https://repo.qst.go.jp/records/6974590b39e40-d15e-4a42-a2e4-205c04878d7a
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2009-05-01 | |||||
| タイトル | ||||||
| タイトル | Role of TNFa in mice exposed to high dose radiation: its mechanisms for radioprotection | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_c94f | |||||
| 資源タイプ | conference object | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Hachiya, Misao
× Hachiya, Misao× Sibata, Tomohiro× Miyamura, Taichi× Akashi, Makoto× 蜂谷 みさを× 柴田 知容× 宮村 太一× 明石 真言 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Exposure to high dose radiation leads to serious radiation injuries. Radiation stimulates the production of tumor necrosis factor a (TNFa) in various cells and tissues. TNFa is a pro-inflammatory cytokine and plays a critical role in inflammation; TNFa-targeted therapies are increasingly used for rheumatic and autoimmune diseases. Furthermore, TNFa induces apoptosis in cells, suggesting that its excess production may lead to damage of tissues and organs in radiation exposure. On the other hand, administration of TNFa has been reported to protect lethally irradiated mice. However, the mechanisms of TNFa for radioprotective effects are not fully understood. In the present study, the wild-type of TNFa (WT) and its knockout (K/O) balb/c mice were subjected to total body g radiation. The survival rates on day 35 (SRs) were 45 and 7% in WT and K/O mice irradiated with 6.5 Gy, respectively. Administration of TNFa increased the survival rate in K/O mice; the SRs were 86 and 43% in these mice administered before and after radiation, respectively. Since autopsy failed to find difference in causes of death between both groups of mice, we compared injuries of bone marrow and small intestine. There was no difference in numbers of white blood cells (WBC) or platelets following to radiation in both mice, whereas radiation markedly reduced these cell numbers. However, 15 days after exposure, numbers of red blood cells (RBC), levels of hemoglobin (Hb), and values of hematocrit (Ht) were significantly reduced in K/O mice with concomitant higher levels of serum iron and lower unsaturated iron binding capacity (UIBC) as compared to those in WT mice. Administration of TNFa significantly improved those in irradiated K/O mice. Assays for crypt microcolony in small intestine showed no difference between both irradiated groups and the similar results were obtained from studies of intestinal cell apoptosis. Interestingly, administration of either TNFa or lipopolysaccharide (LPS) significantly inhibited the apoptosis in WT but not in K/O mice. The serum levels of TNFa were increased following to TNFa challenge in both groups, but that in WT was higher than that in K/O mice. LPS increased the levels of TNFa in WT but not in K/O mice. LPS also increased the levels of interleukin-1a (IL-1a) and IL-1b in both groups of mice, and those levels in WT were higher than that in K/O mice. Administration of IL-1a inhibited radiation-induced apoptosis in small intestine of WT but not K/O mice. However, IL-1b inhibited the apoptosis in both mice. We also studied the expression of Bax and Bcl2 proteins in intestinal crypt cells. Radiation increased the Bax/Bcl2 ratio in both mice. However, administration of TNFa before radiation reduced the ratio in irradiated WT but not in K/O mice. Our results suggest that endogenously-produced TNFa plays important roles in radiation injury. | |||||
| 会議概要（会議名, 開催地, 会期, 主催者等） | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | ＡＡＣＲ 100th Ａｎｎｕａｌ Ｍｅｅｔｉｎｇ 2009 | |||||
| 発表年月日 | ||||||
| 日付 | 2009-04-22 | |||||
| 日付タイプ | Issued | |||||
