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Modified Si-Jun-Zi-Tang Attenuate Airway Inflammation in a Chronic Murine Model of Asthma Via Suppression of mTORC1 Pathway
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A1312 - Modified Si-Jun-Zi-Tang Attenuate Airway Inflammation in a Chronic Murine Model of Asthma Via Suppression of mTORC1 Pathway
Author Block: H. Jin, L. Wang, J. Ye; Hangzhou First People's Hospital, Hangzhou, China.
Background: Modified Si-Jun-Zi-Tang (MSJZT) is frequently used in remmission stage in patients with asthma in traditional Chinese medicine (TCM). Inhibition of mTOR signaling was demonstrated to attenuate key characteristics of asthma. However, it remained unclear whether the beneficial effects of MSJZT on asthma were associated with mTOR inhibition Aims: To investigate the antiasthmatic effects and mechanisms of MSJZT in a chronic mouse model of asthma based on the mTOR signaling pathway. Methods: A chronic mouse model of asthma was established by sensitization and repeated challenge with ovalbumin (OVA) followed with 3 weeks of rest/recovery and then reexposure to ovalbumin. The chemical profile of MSJZT was analyzed by high-performance liquid chromatography (HPLC). The characteristic features of allergic asthma, including airway hyperreactivity, histopathology, and cytokines (IL-4, -5, -13, -17 and INF-γ) in bronchoalveolar lavage fluid (BALF) were examined. Cells from the BALF were analyzed for Treg cells (CD4+CD25+Foxp3+) and Teff cells (CD25+CD4+Foxp3−) expression. The mTORC1 and mTORC2 activities were assessed by phosphorylation of their substrates P-S6 S235/236, P-4E-BP1 S65, P-p70S6K T389, P-mTOR S2481 and P-Akt S473, respectively. Results: The oral administration of MSJZT markedly suppressed airway hyperresponsiveness to aerosolized methacholine and reduced IL-4, IL-5 and IL-13 levels and increased INF-γ levels in the BALF. Histological studies showed that MSJZT markedly decreased inflammatory infiltration in the lung tissues. MSJZT obviously suppressed OVA induced Teff cells but not Treg cells. Furthermore, MSJZT effectively inhibited the mTORC1 activity (as evidenced by reduced substrates S6 S235/236, p70S6K T389 and 4E-BP1 S65 phosphorylation), whereas had limited effects on mTORC2 (as assessed by phosphorylated mTOR S2481 and Akt). Conclusions: MSJZT is effective to attenuate chronic airway inflammation in asthma, the mechanism by which is at least partially via inhibting mTORC1 signaling pathway.
Author Block: H. Jin, L. Wang, J. Ye; Hangzhou First People's Hospital, Hangzhou, China.
Background: Modified Si-Jun-Zi-Tang (MSJZT) is frequently used in remmission stage in patients with asthma in traditional Chinese medicine (TCM). Inhibition of mTOR signaling was demonstrated to attenuate key characteristics of asthma. However, it remained unclear whether the beneficial effects of MSJZT on asthma were associated with mTOR inhibition Aims: To investigate the antiasthmatic effects and mechanisms of MSJZT in a chronic mouse model of asthma based on the mTOR signaling pathway. Methods: A chronic mouse model of asthma was established by sensitization and repeated challenge with ovalbumin (OVA) followed with 3 weeks of rest/recovery and then reexposure to ovalbumin. The chemical profile of MSJZT was analyzed by high-performance liquid chromatography (HPLC). The characteristic features of allergic asthma, including airway hyperreactivity, histopathology, and cytokines (IL-4, -5, -13, -17 and INF-γ) in bronchoalveolar lavage fluid (BALF) were examined. Cells from the BALF were analyzed for Treg cells (CD4+CD25+Foxp3+) and Teff cells (CD25+CD4+Foxp3−) expression. The mTORC1 and mTORC2 activities were assessed by phosphorylation of their substrates P-S6 S235/236, P-4E-BP1 S65, P-p70S6K T389, P-mTOR S2481 and P-Akt S473, respectively. Results: The oral administration of MSJZT markedly suppressed airway hyperresponsiveness to aerosolized methacholine and reduced IL-4, IL-5 and IL-13 levels and increased INF-γ levels in the BALF. Histological studies showed that MSJZT markedly decreased inflammatory infiltration in the lung tissues. MSJZT obviously suppressed OVA induced Teff cells but not Treg cells. Furthermore, MSJZT effectively inhibited the mTORC1 activity (as evidenced by reduced substrates S6 S235/236, p70S6K T389 and 4E-BP1 S65 phosphorylation), whereas had limited effects on mTORC2 (as assessed by phosphorylated mTOR S2481 and Akt). Conclusions: MSJZT is effective to attenuate chronic airway inflammation in asthma, the mechanism by which is at least partially via inhibting mTORC1 signaling pathway.
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