Calcitonin gene-related peptide inhibits chemokine production by human dermal microvascular endothelial cells.
Calcitonin gene-related peptide inhibits chemokine production by human dermal microvascular endothelial cells.
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DOI：
10.1016/j.bbi.2011.02.007
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发表时间：
2011-05
影响因子：
15.1
通讯作者：
Granstein, Richard D.
中科院分区：
文献类型：
--
作者：
Huang, Jing;Stohl, Lori L.;Zhou, Xi;Ding, Wanhong;Granstein, Richard D.
本研究探讨了感觉神经肽降钙素基因相关肽（CGRP）是否抑制真皮微血管内皮细胞释放趋化因子。皮肤血管与含有CGRP的神经相关，表明含有CGRP的神经可以通过对血管的作用来调节皮肤炎症。我们研究了CGRP对人真皮微血管内皮细胞系（HMEC-1）和原代人真皮微血管内皮细胞（pHDMECs）刺激趋化因子产生的影响。HMEC-1细胞和pHDMECs表达CGRP和肾上腺髓质素受体组分的mRNA，CGRP抑制LPS诱导的HMEC-1细胞和pHDMECs产生趋化因子CXCL 8、CCL 2和CXCL 1。受体活性修饰蛋白（RAMP）1/降钙素受体样受体（CL）特异性拮抗剂CGRP 8 -37和BIBN 4096 BS以剂量依赖性方式阻断CGRP的这种作用。CGRP可抑制LPS诱导的HMEC-1细胞IκBα降解和NF-κB与CXCL 1、CXCL 8和CCL 2启动子的结合，而NF-κB激活抑制剂Bay 11-7085可抑制LPS诱导的CXCL 1、CXCL 8和CCL 2的产生。因此，NF-κB通路似乎参与CGRP介导的趋化因子产生抑制。因此，CGRP处理LPS刺激的HMEC-1细胞抑制了它们化学吸引人中性粒细胞和单核细胞的能力。阐明这一途径可能为皮肤炎症的治疗提供新的途径。
This study examined whether the sensory neuropeptide calcitonin gene-related peptide (CGRP) inhibits release of chemokines by dermal microvascular endothelial cells. Dermal blood vessels are associated with nerves containing CGRP, suggesting that CGRP-containing nerves may regulate cutaneous inflammation through effects on vessels. We examined CGRP effects on stimulated chemokine production by a human dermal microvascular endothelial cell line (HMEC-1) and primary human dermal microvascular endothelial cells (pHDMECs). HMEC-1 cells and pHDMECs expressed mRNA for components of the CGRP and adrenomedullin receptors and CGRP inhibited LPS-induced production of the chemokines CXCL8, CCL2, and CXCL1 by both HMEC-1 cells and pHDMECs. The receptor activity-modifying protein (RAMP)1/calcitonin receptor-like receptor (CL)-specific antagonists CGRP8-37 and BIBN4096BS, blocked this effect of CGRP in a dose-dependent manner. CGRP prevented LPS-induced IκBα degradation and NF-κB binding to the promoters of CXCL1, CXCL8 and CCL2 in HMEC-1 cells and Bay 11-7085, an inhibitor of NF-κB activation, suppressed LPS-induced production of CXCL1, CXCL8 and CCL2. Thus, the NF-κB pathway appears to be involved in CGRP-mediated suppression of chemokine production. Accordingly, CGRP treatment of LPS-stimulated HMEC-1 cells inhibited their ability to chemoattract human neutrophils and mononuclear cells. Elucidation of this pathway may suggest new avenues for therapeutic manipulation of cutaneous inflammation.
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影响因子：
3.1
作者：
Gomes, RN;Castro-Faria-Neto, HC;Bozza, MT
通讯作者：
Bozza, MT
影响因子：
7.6
作者：
Amano, Hiroo;Negishi, Izumi;Ishikawa, Osamu
通讯作者：
Ishikawa, Osamu
影响因子：
3.5
作者：
EGUCHI, S;HIRATA, Y;MARUMO, F
通讯作者：
MARUMO, F
影响因子：
6.1
作者：
Clementi, Giuseppe;Caruso, Antonina;Amico-Roxas, Matilde
通讯作者：
Amico-Roxas, Matilde
影响因子：
4.8
作者：
Evans, BN;Rosenblatt, MI;Dickerson, IM
通讯作者：
Dickerson, IM