Dexmedetomidine alleviates airway hyperresponsiveness and allergic airway inflammation through the TLR4/NF‑κB signaling pathway in mice

Mol Med Rep. 2022 Mar;25(3):74. doi: 10.3892/mmr.2022.12590. Epub 2022 Jan 11.

Abstract

Dexmedetomidine (DEX) suppresses inflammatory responses and protects against organ injury. The aim of the present study was to investigate the effect of DEX on airway hyperresponsiveness (AHR) and allergic airway inflammation, as well as its underlying mechanism of action in a murine model of ovalbumin (OVA)‑induced asthma. A total of 30 female BALB/c mice were divided into 6 groups (n=5 mice/group): Control, OVA, OVA + DEX (20, 30 or 50 µg/kg) and OVA + TAK‑242 [a toll‑like receptor 4 (TLR4) inhibitor]. The mice were intraperitoneally injected with 20, 30 or 50 µg/kg DEX 1 h before OVA challenge. AHR to inhaled methacholine (Mch) was measured, and the mice were sacrificed 24 h after the last challenge. AHR following Mch inhalation was measured using the FlexiVent apparatus. Hematoxylin and eosin, periodic acid‑Schiff and Wright‑Giemsa staining was performed to evaluate inflammatory cell infiltration in the lung tissue. The levels of IL‑4, IL‑5 and IL‑13 in the bronchoalveolar lavage fluid were analyzed using ELISA, and their mRNA expression levels in the lung tissue were examined using reverse transcription‑quantitative PCR. The protein expression of TLR4, NF‑κB and phosphorylated (p)NF‑κB in the lung tissue was also detected using immunohistochemistry. In the murine OVA‑induced asthma model, DEX decreased AHR following Mch inhalation and reduced the infiltration of inflammatory cells. IL‑4, IL‑5 and IL‑13 levels in the bronchoalveolar lavage fluid were significantly lower following DEX treatment. Furthermore, DEX treatment inhibited the expression of TLR4, NF‑κB and p‑NF‑κB in the lung tissue and exhibited a similar effect to TAK‑242 treatment. In conclusion, DEX may attenuate AHR and allergic airway inflammation by inhibiting the TLR4/NF‑κB pathway. These results suggested that DEX may represent a potential anti‑inflammatory agent for the treatment and management of patients with asthma.

Keywords: airway hyperresponsiveness; airway inflammation; allergic asthma; dexmedetomidine; toll‑like receptor 4/nuclear factor‑κB pathway.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents
  • Asthma / drug therapy
  • Asthma / etiology
  • Asthma / metabolism*
  • Asthma / pathology
  • Biomarkers
  • Bronchoalveolar Lavage Fluid
  • Cytokines / metabolism
  • Dexmedetomidine / pharmacology*
  • Dexmedetomidine / therapeutic use
  • Disease Models, Animal
  • Disease Susceptibility
  • Female
  • Immunohistochemistry
  • Mice
  • Mucus / metabolism
  • NF-kappa B / metabolism*
  • Respiratory Hypersensitivity / drug therapy
  • Respiratory Hypersensitivity / etiology
  • Respiratory Hypersensitivity / metabolism*
  • Respiratory Hypersensitivity / pathology
  • Signal Transduction / drug effects*
  • Toll-Like Receptor 4 / metabolism*

Substances

  • Anti-Inflammatory Agents
  • Biomarkers
  • Cytokines
  • NF-kappa B
  • Toll-Like Receptor 4
  • Dexmedetomidine

Grants and funding

The present study was supported by the Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (Beijing, China) (grant no. YS202006). Funding was provided for various projects in the experiment, including model establishment, experimental drugs and equipment.