Ccl22/MDC, is a prostaglandin dependent pyrogen, acting in the anterior hypothalamus to induce hyperthermia via activation of brown adipose tissue.
Ccl22/MDC, is a prostaglandin dependent pyrogen, acting in the anterior hypothalamus to induce hyperthermia via activation of brown adipose tissue.
复制标题
DOI：
10.1016/j.cyto.2010.11.017
复制
发表时间：
2011-03
期刊：
影响因子：
3.8
通讯作者：
Bartfai, Tamas
中科院分区：
文献类型：
--
作者：
Osborn, Olivia;Sanchez-Alavez, Manuel;Dubins, Jeffrey S.;Gonzalez, Alejandro Sanchez;Morrison, Brad;Hadcock, John R.;Bartfai, Tamas
CC趋化因子配体22（Ccl 22）是CC趋化因子受体4（Ccr 4）的选择性高亲和力配体。我们已经确定了Ccl 22-Ccr 4对的配体和受体的cDNA编码前下丘脑/视前区（AH/POA）的cDNA文库中的PCR。AH/POA是关键的脑区域，其中内源性热原已被证明作用于温敏神经元以影响棕色脂肪组织（BAT）和其他产热响应组织中的产热。我们表明，AH/POA神经元中存在功能性Ccr 4受体，因为将Ccl 22注射到POA中而不是注射到其他下丘脑核团会诱导核心体温升高（通过无线电遥测测量）。吲哚美辛（5 mg/kg s.c.）预处理显著降低了由POA注射CCl 22（10 ng/0.5ul）引起的体温过高，因此表明这种体温过高是通过环氧合酶激活介导的，因此可能是通过热原前列腺素E2的形成和作用介导的。如18F-FDG -PET成像所示，温度升高涉及呼吸交换率降低和棕色脂肪组织活化增加。我们描述了一种新的作用，在前下丘脑的温度调节，这取决于内源性热原，前列腺素E2的合成的配体CCl 22和它的受体CCr 4。
CC Chemokine ligand 22 (Ccl22) is a selective, high affinity ligand at the CC chemokine receptor 4 (Ccr4). We have identified cDNAs encoding both ligand and receptor of the Ccl22-Ccr4 pair in cDNA libraries of the anterior hypothalamus/preoptic area (AH/POA) by PCR. The AH/POA is the key brain region where endogenous pyrogens have been shown to act on warm sensitive neurons to affect thermogenesis in brown adipose tissue (BAT) and other thermogenically responsive tissues. We show that functional Ccr4 receptors are present in the AH/POA neurons as injection of Ccl22 into the POA but not to other hypothalamic nuclei induces an increase in core body temperature as measured by radiotelemetry. Indomethacin (5mg/kg s.c) pretreatment markedly reduced the hyperthermia evoked by POA injection of Ccl22 (10 ng/0.5ul) and thus suggests that this hyperthermia is mediated through cyclooxygenase activation and thus likely through the formation and action of the pyrogen prostaglandin E2. The temperature elevation involves a decrease in the respiratory exchange ratio and increased activation of the brown adipose tissue as demonstrated by 18F-FDG –PET imaging. We describe a novel role to the ligand Ccl22 and its receptor Ccr4 in the anterior hypothalamus in temperature regulation that depends on the synthesis of the endogenous pyrogen, prostaglandin E2.
登录
查看更多内容
影响因子：
3.3
作者：
Flynn, G;Maru, S;Male, D
通讯作者：
Male, D
影响因子：
3.3
作者：
Leon, LR
通讯作者：
Leon, LR
影响因子：
56.9
作者：
DAVATELIS, G;WOLPE, SD;CERAMI, A
通讯作者：
CERAMI, A
DOI：
10.1073/pnas.0402455101
发表时间：
2004-07-27
影响因子：
11.1
作者：
Corcione, A;Casazza, S;Pistoia, V
通讯作者：
Pistoia, V
影响因子：
15.3
作者：
Bonecchi, R;Bianchi, G;Bordignon, P P;D'Ambrosio, D;Lang, R;Borsatti, A;Sozzani, S;Allavena, P;Gray, P A;Mantovani, A;Sinigaglia, F
通讯作者：
Sinigaglia, F