Abstract:
:The therapeutic potential of the antimicrobial peptide cathelicidin (Camp) administration in sepsis has been widely investigated. However, little is known about the pathophysiological roles of cathelicidin in septic cardiomyopathy. In a lipopolysaccharide (LPS)-induced endotoxaemic model, we found that the mRNA and protein expression of cardiac cathelicidin were induced in C57BL/6J wild-type (WT) mice upon LPS challenge, accompanied by increased circulating cathelicidin levels. We showed that this peptide was mainly derived from neutrophils and monocytes/macrophages. Camp deficiency exacerbated LPS-induced myocardial depression, while the administration of CRAMP (the mature form of mouse cathelicidin) decreased the LPS-induced mortality in a D-galactosamine hydrochloride (D-GalN)-sensitized endotoxin shock model. In vivo, LPS-treated Camp knockout mice had a significant higher protein level of myocardial and circulating tumour necrosis factor-alpha (TNF-α), a major contributing factor to septic cardiomyopathy, compared to LPS-treated WT mice, while CRAMP administration inhibited LPS-induced TNF-α production in the heart and plasma in D-GalN-sensitized endotoxaemic mice. In vitro, CRAMP treatment suppressed LPS-induced Tnf-α mRNA expression in cultured neonatal mouse cardiomyocytes and reduced TNF-α secretion in the culture supernatant. The inhibitory effects of CRAMP on TNF-α production may be related to its neutralizing ability of LPS, since CRAMP application had no effects on another toll-like receptor 4 ligand paclitaxel-induced Tnf-α mRNA expression in cardiomyocytes. These findings suggest that LPS-induced cathelicidin protects the heart against myocardial depression partly through the inhibition of TNF-α production via neutralizing LPS.
journal_name
Clin Exp Pharmacol Physioljournal_title
Clinical and experimental pharmacology & physiologyauthors
Zhai T,Zhang J,Zhang Y,Wu Ydoi
10.1111/1440-1681.13234subject
Has Abstractpub_date
2020-04-01 00:00:00pages
677-686issue
4eissn
0305-1870issn
1440-1681journal_volume
47pub_type
杂志文章abstract::1. Insulin-like growth factor (IGF)-I has acute effects on cardiovascular function, including a well-characterized vasodilator response in isolated arteries. In addition to increasing the release of nitric oxide, IGF-I also has effects on a variety of other signalling pathways that affect vascular tone, in particular ...
journal_title:Clinical and experimental pharmacology & physiology
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journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.1991.tb01419.x
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abstract::1. The antitumour effect of orally administered cordycepin, a component isolated from water extracts of Cordyceps sinensis, was examined in mice inoculated with B16 melanoma (B16-BL6) cells. 2. B16-BL6 (1 x 10(6)) cells were inoculated subcutaneously into the right footpad of mice. At 2 weeks after the cell inoculatio...
journal_title:Clinical and experimental pharmacology & physiology
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journal_title:Clinical and experimental pharmacology & physiology
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doi:10.1111/1440-1681.13283
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更新日期:2008-07-01 00:00:00
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pub_type: 杂志文章
doi:10.1111/j.1440-1681.1990.tb01273.x
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journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
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更新日期:2016-03-01 00:00:00