Influence of toll-like receptor-4 antagonist on bacterial load of asthma in Swiss albino mice: targeting TLR4/MD2 complex pathway

Environ Sci Pollut Res Int. 2023 Mar;30(12):32854-32865. doi: 10.1007/s11356-022-24521-4. Epub 2022 Dec 6.

Abstract

Air pollution and environmental issues significantly impact life, resulting in the emergence and exacerbation of allergic asthma and other chronic respiratory infections. The main objective of this study is to suppress allergic asthma by TAK-242 from lipopolysaccharide-induced airway inflammation primarily stimulating toll-like receptor-4, and also to determine the potential mechanism of asthma eradication. The TAK-242 anti-allergic action was assured through the ovalbumin murine model of asthma via bronchial hyperresponsiveness and inflammation of the respiration tract in a pre-existing allergic inflammation paradigm. Swiss albino mice were sensitized and then challenged by ovalbumin and lipopolysaccharide for 5 days straight. TAK-242 reaction was assessed by inflammatory cytokines, and inflammatory cell count was determined from blood serum and bronchoalveolar lavage fluid, as well as group-wise regular weight assessments. After ovalbumin, lipopolysaccharide infusion, toll-like receptor-4 agonists caused a substantial increase in airway hyperresponsiveness, specific cellular inflammation, histological alterations, and immune mediator synthesis, as well as dose-related body-weight variations. A decrease in lipopolysaccharide-induced leukocyte count and Th1/Th17 related cytokines, TNF-α, and IL-6 expression through the ELISA study was particularly noticeable. Finally in treated groups, TAK-242, a TLR4/MD2 complex inhibitor, reduced airway inflammation and histopathological changes, cytokine expression, and body-weight management. TAK-242 has been found in an ovalbumin allergic asthma model to be a potential inhibitor of lipopolysaccharide-induced respiratory infection.

Keywords: Asthma; Immunity; Inflammation; Lipopolysaccharide; Ovalbumin; TAK-242; TLR4.

MeSH terms

  • Animals
  • Asthma* / chemically induced
  • Asthma* / drug therapy
  • Bacterial Load
  • Bronchoalveolar Lavage Fluid
  • Cytokines
  • Disease Models, Animal
  • Inflammation / complications
  • Lipopolysaccharides* / pharmacology
  • Lung / pathology
  • Mice
  • Mice, Inbred BALB C
  • Ovalbumin
  • Toll-Like Receptor 4 / metabolism

Substances

  • ethyl 6-(N-(2-chloro-4-fluorophenyl)sulfamoyl)cyclohex-1-ene-1-carboxylate
  • Lipopolysaccharides
  • Ovalbumin
  • Toll-Like Receptor 4
  • Cytokines
  • Tlr4 protein, mouse