CRTH2 antagonist ameliorates airway inflammation in rats with asthma / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the effect of prostaglandin D2 receptor antagonists on the airway inflammation in rats with asthma.</p><p><b>METHODS</b>Forty male SD rats were randomly divided into four groups: Group A (normal control), Group B (asthma group), Group C (CRTH2 antagonist BAYu3405 treatment group), Group D (DP1 antagonist BWA868C treatment group). Asthma was induced by ovalbumin (OVA) challenge. The rats in each group were sacrificed 24 h after the last challenge of OVA.DP1/CRTH2 receptors on eosinophils (EOS) were measured by radiological binding assay (RBA). The left lungs were used for histological examinations and bronchoalveolar lavage fluid (BALF) was collected from the right lungs. The total cell numbers, EOS absolute count and differential cell counts in BALF were performed. Serum concentrations of IL-4, 5 and IFN-gamma were measured by ELISA.</p><p><b>RESULTS</b>Rats in BAYu3405 treatment group showed profoundly decreased infiltrates of EOS and lymphocytes in the wall of bronchus when compared with those of asthma group and BWA868C treatment group. Serum concentrations of IFN-gamma in rats of BAYu3405 treatment group increased, but IL-4 and IL-5 decreased significantly when compared with those in rats of asthma group and BWA868C treatment group (P<0.01), and BALF EOS count was decreased significantly (P<0.01). Peripheral blood EOS count was higher than that in rats of normal control group, but was not significantly different from that in rats of asthma group and BWA868C treatment group. The combining capacity of CRTH2 and DP total combining capacity on EOS in asthma group, BAYu3405 treatment group and BWA868C treatment group were significantly higher than those in Group A (P<0.01). There was no significant difference in DP1 among all the groups (P>0.05).</p><p><b>CONCLUSION</b>CRTH2, but not DP1 antagonist can effectively ameliorate airway inflammation in rats with asthma.</p>

Changes of prostaglandin D2 receptor on T cells in peripheral blood of children with asthma / 中国当代儿科杂志

<p><b>OBJECTIVE</b>Chronic airway inflammation is associated with the polarization of TH2 cells in asthma. Prostaglandin D2 (PGD2) plays an important role in the polarization of TH2 cells. This study aimed to investigate the changes of PGD2 receptors (DP1/CRTH2) on T lymphocytes and their significance in asthma.</p><p><b>METHODS</b>Seventy-two children with asthma were assigned to two groups: acute attack (n=42) and remission (n=30). Thirty-five healthy children were used as the control group. Plasma levels of TH2 cytokines IL-4 and IL-5, and TH1 cytokine INF-gamma were detected using ELISA. Radiological binding assay (RBA) was used to measure the contents of DP1/CRTH2 receptors on T cells in peripheral blood (PPB).</p><p><b>RESULTS</b>The total combining contents of DP and CRTH2 on T cells in PPB in the acute attack and the remission groups were significantly higher than those in the control group (p<0.01). There was no significant difference in the DP1 content among the three groups. Serum levels of IL-4 and IL-5 significantly increased (p<0.01), in contrast, serum levels of TH1 cytokine IFN-gamma were significantly reduced in the acute attack and the remission groups compared with those in the control group (p<0.01).</p><p><b>CONCLUSIONS</b>The total combining contents of DP and CRTH2 on T cells increased, serum levels of TH2 cytokines also increased, but serum levels of TH1 cytokine decreased significantly in the acute attack and the remission phases in children with asthma. This showed that a polarization of TH2 cells occurred in children with asthma and suggested that CRTH2 antagonism may be a new target for the treatment of asthma.</p>