Background: Electroacupuncture (EA) has been shown to attenuate airway inflammation in asthmatic mice;however, the underlying mechanism is not fully understood. Studies have shown that EA can significantly increase th...Background: Electroacupuncture (EA) has been shown to attenuate airway inflammation in asthmatic mice;however, the underlying mechanism is not fully understood. Studies have shown that EA can significantly increase the inhibitory neurotransmitter γ-aminobutyric acid (GABA) content in mice, and can also increase the expression level of GABA type A receptor (GABAAR). Furthermore, activating GABAAR may relieve inflammation in asthma by suppressing toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-kappa B (NF-κB) signaling pathway. Therefore, this study aimed to investigate the role of GABAergic system and TLR4/MyD88/NF-κB signaling pathway in asthmatic mice treated with EA. Methods: A mouse model of asthma was established, and a series of methods including Western blot and histological staining assessment were employed to detect the level of GABA, and expressions of GABAAR and TLR4/MyD88/NF-κB in lung tissue. In addition, GABAAR antagonist was used to further validate the role and mechanism of GABAergic system in mediating the therapeutic effect of EA in asthma. Results: The mouse model of asthma was established successfully, and EA was verified to alleviate airway inflammation in asthmatic mice. The release of GABA and the expression of GABAAR were significantly increased in asthmatic mice treated with EA compared with untreated asthmatic mice ( P < 0.01), and the TLR4/MyD88/NF-κB signaling pathway was down-regulated. Moreover, inhibition of GABAAR attenuated the beneficial effects of EA in asthma, including the regulation of airway resistance and inflammation, as well as the inhibitory effects on TLR4/MyD88/NF-κB signaling pathway. Conclusion: Our findings suggest that GABAergic system may be involved in mediating the therapeutic effect of EA in asthma, possibly by suppressing the TLR4/MyD88/NF-κB signaling pathway.展开更多
Background Disequilibrium of Th1/Th2 is known as an important cause of allergic asthma with a biased Th2 type response. It has been shown that lipopolysaccharide （LPS） administration during post-sensitization modifi...Background Disequilibrium of Th1/Th2 is known as an important cause of allergic asthma with a biased Th2 type response. It has been shown that lipopolysaccharide （LPS） administration during post-sensitization modified the inflammation of asthma via upregulating the Thl response that decrease the Th2 immunity. We would like to know if, during pre-sensitization, the elevated Thl response is necessary for LPS exposure to modify the asthmatic response. Methods During pre- or post-sensitization, 40 IJg LPS were intraperitoneal injected （i.p.） to asthmatic mice sensitized and challenged by Dermatophagoides farinae （D. farinea）. Inflammation was assessed by examining bronchoalveolar lavage fluid （BALF） for the number and identity of cells and by cytokine titers measured by ELISA. Semi-quantified RT-PCR was used to evaluate the level of Toll-like receptor 4 （TLR4） mRNA in dendritic cells （DCs） from bone marrow （BMDCs）. Results These investigations demonstrated that LPS exposure during pre-sensitization inhibited the Th2 cytokine and inflammatory infiltration, the same as with LPS exposure during post-sensitization in allergic asthma mice. Contrary to post-sensitization LPS exposure, the Thl cytokines were not upregulated by pre-sensitization with LPS. Finally, the study failed to show any significant difference between TLR4 mRNA expressed in BMDCs with the two times of LPS exposure. Conclusions Our data suggest that elevated Thl immunity is not required for the modification of the Th2 response induced by LPS exposure during pre-sensitization in asthmatic mice and that pre-sensitization differs from post-sensitization. Immune modulation with treatment is independent of TLR4 expression in BMDCs. This study implicates a potential wav to protect from allergic disease and an inflammatory response.展开更多
基金supported a grant from the Scientific Research Fund of China–Japan Friendship Hospital(No.2017-RC-3).
文摘Background: Electroacupuncture (EA) has been shown to attenuate airway inflammation in asthmatic mice;however, the underlying mechanism is not fully understood. Studies have shown that EA can significantly increase the inhibitory neurotransmitter γ-aminobutyric acid (GABA) content in mice, and can also increase the expression level of GABA type A receptor (GABAAR). Furthermore, activating GABAAR may relieve inflammation in asthma by suppressing toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-kappa B (NF-κB) signaling pathway. Therefore, this study aimed to investigate the role of GABAergic system and TLR4/MyD88/NF-κB signaling pathway in asthmatic mice treated with EA. Methods: A mouse model of asthma was established, and a series of methods including Western blot and histological staining assessment were employed to detect the level of GABA, and expressions of GABAAR and TLR4/MyD88/NF-κB in lung tissue. In addition, GABAAR antagonist was used to further validate the role and mechanism of GABAergic system in mediating the therapeutic effect of EA in asthma. Results: The mouse model of asthma was established successfully, and EA was verified to alleviate airway inflammation in asthmatic mice. The release of GABA and the expression of GABAAR were significantly increased in asthmatic mice treated with EA compared with untreated asthmatic mice ( P < 0.01), and the TLR4/MyD88/NF-κB signaling pathway was down-regulated. Moreover, inhibition of GABAAR attenuated the beneficial effects of EA in asthma, including the regulation of airway resistance and inflammation, as well as the inhibitory effects on TLR4/MyD88/NF-κB signaling pathway. Conclusion: Our findings suggest that GABAergic system may be involved in mediating the therapeutic effect of EA in asthma, possibly by suppressing the TLR4/MyD88/NF-κB signaling pathway.
文摘Background Disequilibrium of Th1/Th2 is known as an important cause of allergic asthma with a biased Th2 type response. It has been shown that lipopolysaccharide （LPS） administration during post-sensitization modified the inflammation of asthma via upregulating the Thl response that decrease the Th2 immunity. We would like to know if, during pre-sensitization, the elevated Thl response is necessary for LPS exposure to modify the asthmatic response. Methods During pre- or post-sensitization, 40 IJg LPS were intraperitoneal injected （i.p.） to asthmatic mice sensitized and challenged by Dermatophagoides farinae （D. farinea）. Inflammation was assessed by examining bronchoalveolar lavage fluid （BALF） for the number and identity of cells and by cytokine titers measured by ELISA. Semi-quantified RT-PCR was used to evaluate the level of Toll-like receptor 4 （TLR4） mRNA in dendritic cells （DCs） from bone marrow （BMDCs）. Results These investigations demonstrated that LPS exposure during pre-sensitization inhibited the Th2 cytokine and inflammatory infiltration, the same as with LPS exposure during post-sensitization in allergic asthma mice. Contrary to post-sensitization LPS exposure, the Thl cytokines were not upregulated by pre-sensitization with LPS. Finally, the study failed to show any significant difference between TLR4 mRNA expressed in BMDCs with the two times of LPS exposure. Conclusions Our data suggest that elevated Thl immunity is not required for the modification of the Th2 response induced by LPS exposure during pre-sensitization in asthmatic mice and that pre-sensitization differs from post-sensitization. Immune modulation with treatment is independent of TLR4 expression in BMDCs. This study implicates a potential wav to protect from allergic disease and an inflammatory response.
