896:
Celastrol Alleviates Airway Hyperresponsiveness by Downregulating Th17 in Obese Asthmatic Mice
Monday, March 5, 2018: 2:15 PM
S230EF (Convention Center)
Weixi Zhang, MD, PhD, ,
RATIONALE: Obese asthma subjects demonstrate more severe airway hyperresponsiveness (AHR) than non-obese asthma patients. The former is also steroid-resistant, partially due to inflammation induced by Th17 cells. Celastrol was reported to inhibit the function of Th17 cells. We thought to explore the effect of Celastrol on AHR of obese asthmatic mice and identify its underlying mechanism.

METHODS: Obese, ovalbumin-induced asthma (DIO-OVA) model was established by feeding mice with high fat diet for 16 weeks and sensitizing intraperitoneally with OVA on days 1 and 13 starting from week 12, followed by aerosol OVA challenge for 7 consecutive days on week 16. Celastrol-treated-DIO-OVA mice received oral Celastrol (10mg/kg) 30 min before each challenge. Sham control group received normal diet and normal saline in sensitization and challenge phases. Plethysmography was performed to measure airway resistance (Rn) and PC20 of methacholine (MCh) challenge. Flow cytometry was used to examine the splenic Th17 cell population. Serum IL-17 levels of Celastrol-treated and control groups were measured by ELISA.

RESULTS: Comparing to control, Celastrol-treated DIO-OVA mice showed significant reduction of Rn (0.41 ± 0.04 vs 0.66 ± 0.10 cmH2O/mL/s, P<0.01). A correspondent increase of PC20 of MCh was noticed. Moreover, Celastrol treatment led to a significant decrease of splenic Th17 cell frequency (2.48 ± 1.14% vs 13.55 ± 2.12%, P<0.01) and serum Th17 concentration (66.24 ± 8.21 vs 145.19 ± 7.61 pg/ml, P<0.01).

CONCLUSIONS: Celastrol reduces airway hyperresonsiveness of obese, OVA-induced asthma mice. This potential therapeutic effect is possibly due to the inhibition of Th17 cell numbers and their Th17 production.