The use of the antimicrobial peptide piscidin (PCD)-1 as a novel anti-nociceptive agent

被引:43
作者
Chen, Wu-Fu [1 ,2 ,3 ]
Huang, Shi-Ying [4 ]
Liao, Chang-Yi [5 ]
Sung, Chun-Sung [6 ,7 ]
Chen, Jyh-Yih [8 ]
Wen, Zhi-Hong [5 ,9 ,10 ]
机构
[1] Kaohsiung Chang Gung Mem Hosp, Dept Neurosurg, Kaohsiung 833, Taiwan
[2] Chang Gung Univ, Coll Med, Kaohsiung 833, Taiwan
[3] Kaohsiung Chang Gung Mem Hosp, Ctr Parkinsons Dis, Kaohsiung 833, Taiwan
[4] Natl Sun Yat Sen Univ, Ctr Neurosci, Kaohsiung 804, Taiwan
[5] Natl Sun Yat Sen Univ, Dept Marine Biotechnol & Resources, Kaohsiung 804, Taiwan
[6] Taipei Vet Gen Hosp, Dept Anesthesiol, Taipei 112, Taiwan
[7] Natl Yang Ming Univ, Sch Med, Taipei 112, Taiwan
[8] Acad Sinica, Inst Cellular & Organism Biol, Marine Res Stn, Jiaushi 262, Ilan, Taiwan
[9] Natl Sun Yat Sen Univ, Dept Marine Biotechnol & Resources, Marine Biomed Lab, Kaohsiung 804, Taiwan
[10] Natl Sun Yat Sen Univ, Dept Marine Biotechnol & Resources, Ctr Translat Biopharmaceut, Kaohsiung 804, Taiwan
关键词
Piscidin-1; Antimicrobial peptide; Chronic constriction injury; Neuropathic pain; Allodynia; Hyperalgesia; NITRIC-OXIDE SYNTHASE; HYBRID STRIPED BASS; ATTENUATES NOCICEPTIVE RESPONSES; CHRONIC CONSTRICTION INJURY; PERIPHERAL-NERVE INJURY; FORMOSAN SOFT CORAL; NEUROPATHIC PAIN; TRANSFORMING GROWTH-FACTOR-BETA-1; SPINAL-CORD; RAT MODEL;
D O I
10.1016/j.biomaterials.2015.02.069
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
The antimicrobial peptide piscidin (PCD)-1 has been reported to have antibacterial and immunomodulatory functions. Here, we investigated the anti-neuropathic properties of PCD-1, in order to determine its potential as a compound to alleviate pain. Treatment with PCD-1 suppressed the inflammatory proteins COX-2 and iNOS in murine macrophage (RAW264.7) and microglial (BV2) cell lines stimulated by lipopolysaccharide (LPS). For studies of the effect of PCD-1 in vivo, mononeuropathy in rats was induced by chronic constriction injury (CCI), and the resulting anti-nociceptive behaviors were compared between CCI controls and CCI rats given intrathecal injections of PCD-1. Much like gabapentin, PCD-1 exerts anti-nociceptive effects against thermal hyperalgesia, with a median effective dose (ED50) of 9.5 mu g in CCI rats. In CCI rats, PCD-1 exerted effects against mechanical and cold allodynia, thermal hyperalgesia, and weight-bearing deficits. Furthermore, CC-mediated activation of microglia and astrocytes in the dorsal horn of the lumbar spinal cord were decreased by PCD-1. In addition, PCD-1 suppressed up-regulation of interleukin-1 beta (IL-1 beta) and phosphorylated mammalian target of rapamycin (phospho-mTOR) in CCI rats. Finally, CU-induced down-regulation of transforming growth factor-beta 1 (TGF-beta 1) in rats was attenuated by injection of PCD-1. Taken together, the present findings demonstrate that the marine antimicrobial peptide PCD-1 has anti-nociceptive effects, and thus may have potential for development as an alternative pain-alleviating agent. (C) 2015 Elsevier Ltd. All rights reserved.
引用
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页码:1 / 11
页数:11
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