Abstract

To investigate the effect of budesonide (BUD) on thymic stromal lymphopoietin receptor (TSLPR) of dendritic cells (DCs) in OVA-induced mouse asthma models and to explore the mechanisms by studying the effect of BUD on function of DCs from the model. Eighteen BALB/c female mice were randomly divided into a control group, an asthma group and a BUD intervention group, with 6 mice in each group. Mice were sensitized and challenged with ovalbumin (OVA) to establish the asthmatic model. The bronchoalveolar lavage fluid (BALF) and DCs of spleen from the 3 groups were harvested and the supernatants of BALF and DCs were analyzed for levels of TSLP and TSLPR, respectively, by commercially available ELISA kit. The percentage of eosinophils (EOS) in BALF was counted. The expression of CD₄₀, CD₈₀ and CD₈₆ in DCs was detected by FACS. The DCs were then washed, and co-cultured in vitro with autologous T cells purified by a nylon cotton column. The supernatants of DC-T co-culture were collected after 72 h incubation, and analyzed for levels of interleukin-5 (IL-5) and interferon-γ (IFN-γ) by ELISA. The levels of TSLP in BALF and TSLPR in DCs from the asthma group were significantly increased compared with the control group [(44.0 ± 5.1) ng/L vs (14.2 ± 3.6) ng/L, P < 0.01 and (19.7 ± 2.2) ng/L vs (10.4 ± 1.2) ng/L, P < 0.05, respectively]. The expression of CD₄₀, CD₈₀ and CD₈₆ of DCs and IL-5 in the culture supernatants of DC-T co-culture was significant up-regulated in the asthma group compared with the control group (P < 0.05). Furthermore, the addition of BUD reduced the expression of CD₄₀, CD₈₀, CD₈₆, TSLPR in DCs, IL-5 in the culture supernatants of DC-T co-culture, TSLP and EOS in BALF. The level of INF-γ in the DC-T co-culture supernatants of the 3 groups did not achieve statistical significance (F = 0.82, P > 0.05). These results demonstrate that the therapeutic activity of BUD in asthmatic mice may be related to modulation of Th1 and Th2 cell functions and this effect is probably mediated through the TSLP-DC pathway.

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