Modulation of Toll-like signal path of allergic asthma by CpG-ODNs from Bordetella pertussis / 药学学报

ABSTRACT

This study focused on prevention and treatment of acute and chronic asthma by oligonucleotides containing unmethylated CpG motifs (CpG-ODNs). Acute and chronic asthma models of mice were made by sensitizing and inhaling ovalbumin (OVA); The number of white blood cells (WBC) and eosnophils (EOS) in bronchoalveolar lavage fluid (BALF) was counted and the concentration of cytokines and vascular endothelial growth factor (VEGF) was examined in BALF by ELISA kit. After that, TLR-9 mRNA was detected in mice spleen cells by reverse transcription polymerase chain reaction (RT-PCR) and TLR-9 protein was determined in mice lung tissues by Western blotting. Compared with acute asthma models of mice, WBC in BALF decreased obviously in the groups of Bordetella pertussis, CpG-ODNs and seq A to seq I which were administrated by both of intragastric (ig) and intraperitoneal (ip) injection group, EOS decreased obviously in Bordetella pertussis, CpG+ and seq A to seq D ig groups, and in all ip administrating groups, although it was not effective in the groups of seq E to seq I. In chronic asthma models of mice, IFN-gamma increased ((1) control 176.45 +/- 23.46 pg x mL(-1); (2) model 174.11 +/- 22.71 pg x mL(-1); (3) CpG+ ip 220.56 +/- 15.42 pg x mL(-1); (4) seq A ip 225.23 +/- 21.60 pg x mL(-1)) and IL-4 decreased obviously (1) control 66.91 +/- 5.81 pg x mL(-1); (2) model 81.02 +/- 11.24 pg x mL(-1); (3) CpG+ ip 63.99 +/- 6.09 pg x mL(-1); (4) seq A ip 62.75 +/- 10.03 pg x mL(-1)) in the BALF of CpG+ and seq A ip group, although VEGF was not changed in this research. And also, TLR-9 mRNA in spleen cells (TLR-9/GAPDH (1) control 0.62 +/- 0.13; (2) model 0.66 +/- 0.17; (3) CpG+ ip 1.46 +/- 0.26; (4) seq A ip 1.42 +/- 0.34) and TLR-9 protein in lung tissues (TLR-9/beta-actin (1) control 0.63 +/- 0.16; (2) model 0.61 +/- 0.07; (3) CpG+ ip 1.15 +/- 0.25; (4) seq A ip 1.03 +/- 0.29) both increased in ip groups, but the change was not significant in ig group. The study confirms that CpG-ODNs and seq A could inhibit airway inflammation remarkably, this mechanism might be related with regulating Th1/Th2 balance and controlling the expression of TLR-9.