Effects of antagonistic peptide specifically binding to second extracellular loop of CCR5 on inflammatory cell infiltration and TNF-α expression in lung tissues of asthmatic mice induced by OVA / 中国病理生理杂志

ABSTRACT

AIM: To investigate the effects of antagonistic peptide specifically binding to the second extracellular loop of CC chemokine receptor 5 (CCR5) on inflammatory cell infiltration and TNF-α expression in lung tissues of asthmatic mice.METHODS: The asthmatic model of BALB/c mice was induced by ovalbumin (OVA) and the optimal sensitization concentration of OVA was screened.After modeling, the mice were intervened by gradual concentrations of antagonistic peptide via tail-vein injection.The pathocytological analysis and grading were performed in the lung tissues with HE staining.The expression of TNF-α at mRNA and protein levels in the lung tissues was determined by real-time PCR and Western blot.RESULTS: The optimal concentration of OVA was 500 mg/L (0.1 mL) as this concentration of OVA stably induced moderate degree of inflammation in the BALB/c mice.Treatment with different concentrations (1.5 g/L, 2.5 g/L and 3.5 g/L) of antagonistic peptide at 0.2 mL through tail-vein injection inhibited the expression of TNF-α, and markedly reduced the degree of inflammation in the lung tissues.The optimal concentration of antagonistic peptide was 2.5 g/L as the lung inflammation degree in 2.5 g/L group alleviated by 2 grades, and the number of inflammatory cells was also significantly reduced.Moreover, the mRNA expression abundance of TNF-α was nearly decreased by 90%, and the protein expression of TNF-α was decreased by 70% compared with model group.Meanwhile, the use of antagonistic peptide at 2.5 g/L before OVA stimulation confirmed the preventive function to some degree.In this group, the lung inflammation degree alleviated by 1 grade, and the expression of TNF-α at both mRNA and protein levels decreased by nearly 50%.CONCLUSION: The antagonistic peptide of CCR5 effectively inhibits the expression of TNF-α and relieves the inflammation in the asthmatic mouse lung tissues in a concentration-dependent manner.