[Experimental study on the antagonistic activity of cationic multi-peptide mastoparan-1 against lipopolysaccharide].
Zhonghua Shao Shang Za Zhi
; 21(3): 189-92, 2005 Jun.
Article
em Zh
| MEDLINE
| ID: mdl-15996281
ABSTRACT
OBJECTIVE:
To explore the mechanism of cationic multi-peptide mastoparan-1 (MP-1) on the protection of mice from lipopolysaccharide (LPS) challenge.METHODS:
Thirty Kunming mice were divided randomly into MP-1, injury, protection groups with 10 mice in each group. The mice in MP-1 group were injected with 3 mg/kg MP-1 by tail vein, while those in injury group were injected with 20 mg/kg LPS by tail vein, and those in protection group 3 mg/kg MP-1 within 20 seconds after 20 mg/kg LPS injection were injected. The effects of MP-1 on the protection of mice from LPS challenge were observed. In vitro, the affinity of MP-1 and PMB to LPS was compared by biosensor and FAST fit construct and expressed as Kd. And the neutralizing activity of MP-1 and PMB in dose of 5, 10, 20, 40 micromol/L on LPS (2 microg/L) was detected by dynamic turbidimetric limulus test with LPS neutralizing 0 micromol/L MP-1 and PMB as control. The mRNA expression levels of TLR4, TNF-alpha and IL-6 in murine peritoneal macrophages (PM phi) after exposure to LPS (100 ng/ml) were assayed by RT-PCR.RESULTS:
MP-1 could significantly protect mice from LPS challenging with protection rate of 90%. In vitro, MP-1 had a high affinity (Kd value 484.0 nmol/L) and neutralizing ability with LPS, but it was lower than that of PMB (Kd value 18.9 nmol/L). The neutralizing effect of 20 and 40 micromol/L MP-1 was obviously stronger than that in 0 micromol/L (P < 0.01). MP could obviously inhibit the expression of TLR4, TNF-alpha and IL-6 mRNA in LPS-stimulated murine PM phi.CONCLUSION:
MP-1 can evidently protect mice from lethal LPS challenge, and the mechanism might be related to the activity of MP-1 which binding and neutralizing LPS, blocking the combination LPS with its receptors. So the murine macrophage activation induced by LPS was inhibited.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Venenos de Vespas
/
Lipopolissacarídeos
/
Macrófagos Peritoneais
Limite:
Animals
Idioma:
Zh
Ano de publicação:
2005
Tipo de documento:
Article