Spleen-derived interleukin-10 downregulates the severity of high-fat diet-induced non-alcoholic fatty pancreas disease.
Spleen-derived interleukin-10 downregulates the severity of high-fat diet-induced non-alcoholic fatty pancreas disease.
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DOI：
10.1371/journal.pone.0053154
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Yoshimatsu H
中科院分区：
文献类型：
--
作者：
Gotoh K;Inoue M;Shiraishi K;Masaki T;Chiba S;Mitsutomi K;Shimasaki T;Ando H;Fujiwara K;Katsuragi I;Kakuma T;Seike M;Sakata T;Yoshimatsu H
肥胖与全身低度炎症相关，是非酒精性脂肪胰腺病（NAFPD）的危险因素，但这些关联的分子机制尚不清楚。白细胞介素 (IL)-10 是一种有效的抗炎细胞因子，在急性胰腺炎期间释放，已知可通过下调促炎介质的释放来限制炎症反应。抑制胰腺炎的 IL-10 的起源尚未被研究。由于已知肥胖会减少脾脏中促炎细胞因子的表达，因此我们检查了脾源性 IL-10 是否调节高脂肪 (HF) 饮食诱导的肥胖引起的 NAFPD。进行了以下研究：1) 在饲喂 HF 饮食的雄性小鼠中检查了脾脏对 IL-10 的诱导作用； 2) 测定甘油三酯含量、促炎和抗炎细胞因子的表达以及 M1 和 M2 巨噬细胞的浸润，以评估饲喂 HF 饮食的脾切除 (SPX) 治疗小鼠胰腺中的异位脂肪积累和炎症反应； 3)将外源性IL-10全身给予SPX处理的肥胖小鼠，并评估由SPX引起的发病机制； 4) 用 SPX 治疗 IL-10 敲除 (IL-10KO) 小鼠，并研究胰腺中的异位脂肪沉积和炎症状况。肥胖会损害脾脏合成细胞因子（包括 IL-10）的能力。 SPX 加重了 HF 饮食诱导的肥胖小鼠胰腺中的脂肪积累和炎症反应，而全身施用 IL-10 可以抑制这些影响。此外，SPX对IL-10KO小鼠胰腺中的脂肪沉积和炎症反应几乎没有影响。我们的研究结果表明，肥胖会减少脾脏产生 IL-10，而脾脏来源的 IL-10 可能会预防 NAFPD 的发生。
Obesity is associated with systemic low-grade inflammation and is a risk factor for non-alcoholic fatty pancreas disease (NAFPD), but the molecular mechanisms of these associations are not clear. Interleukin (IL)-10, a potent anti-inflammatory cytokine, is released during acute pancreatitis and is known to limit inflammatory responses by downregulating the release of proinflammatory mediators. The origin of IL-10 that suppresses pancreatitis has not been investigated. Since obesity is known to reduce expression of proinflammatory cytokines in the spleen, we examined whether spleen-derived IL-10 regulates NAFPD caused by high-fat (HF) diet-induced obesity. The following investigations were performed: 1) IL-10 induction from spleen was examined in male mice fed a HF diet; 2) triglyceride content, expression of pro- and anti-inflammatory cytokines and infiltration of M1 and M2 macrophages were determined to evaluate ectopic fat accumulation and inflammatory responses in the pancreas of splenectomy (SPX)-treated mice fed HF diet; 3) exogenous IL-10 was systemically administered to SPX-treated obese mice and the resulting pathogenesis caused by SPX was assessed; and 4) IL-10 knockout (IL-10KO) mice were treated with SPX and ectopic fat deposition and inflammatory conditions in the pancreas were investigated. Obesity impaired the ability of the spleen to synthesize cytokines, including IL-10. SPX aggravated fat accumulation and inflammatory responses in the pancreas of HF diet-induced obese mice and these effects were inhibited by systemic administration of IL-10. Moreover, SPX had little effect on fat deposition and inflammatory responses in the pancreas of IL-10KO mice. Our findings indicate that obesity reduces IL-10 production by the spleen and that spleen-derived IL-10 may protect against the development of NAFPD.
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影响因子：
29.4
作者：
Bachem, MG;Schneider, E;Adler, G
通讯作者：
Adler, G
代谢综合征的小鼠模型；内脏脂肪组织的增加先于高脂饮食喂养的雄性KK/TA小鼠的脂肪肝和胰岛素抵抗的发展。
影响因子：
2.4
作者：
Akagiri, Satomi;Naito, Yuji;Ichikawa, Hiroshi;Mizushima, Katsura;Takagi, Tomohisa;Handa, Osamu;Kokura, Satoshi;Yoshikawa, Toshikazu
通讯作者：
Yoshikawa, Toshikazu
影响因子：
17.1
作者：
Navina S;Acharya C;DeLany JP;Orlichenko LS;Baty CJ;Shiva SS;Durgampudi C;Karlsson JM;Lee K;Bae KT;Furlan A;Behari J;Liu S;McHale T;Nichols L;Papachristou GI;Yadav D;Singh VP
通讯作者：
Singh VP
DOI：
10.1007/bf01605976
发表时间：
1992-01-01
期刊：
VIRCHOWS ARCHIV A-PATHOLOGICAL ANATOMY AND HISTOPATHOLOGY
影响因子：
--
作者：
KLOPPEL, G;MAILLET, B
通讯作者：
MAILLET, B
DOI：
10.1152/ajprenal.00107.2011
发表时间：
2011-10-01
影响因子：
4.2
作者：
Andres-Hernando, Ana;Altmann, Christopher;Faubel, Sarah
通讯作者：
Faubel, Sarah