Evaluation of bronchial inflammatory response via expression of NF-κB & IL-1β in mice airways by TAK-242 and LPS administration: Targeting TLR4/MD2 signalling pathway

Abstract

Optimization of animal model of asthma via toll like receptors-4 (TLR4) activation for bacterial exacerbation of asthma. LPS contributes to asthma exacerbations. Ovalbumin protein sensitization & challenge were examined after LPS exposure. Present research aimed, TLR4 stimulation mediated TLR4/MD2 complex formation is inhibited by TAK-242, a newer compound, for bacterial asthma management in a mouse model. Swiss Albino mice were induced with OVA (10µg, i.p. and 50 µg, i.n.) and LPS (20 µg, i.p. and 4 µg, i.n.), stimulates TLR4 receptor mediated TLR4-MD2 complex formation in toxic groups. Animals were sensitized (i.p.) on 0, 7th and 14th day and challenged (i.n.) followed by TAK-242 treatment (0.1 mg/kg, 1 mg/kg &10 mg/kg i.p.) given on 21st and 22nd days, followed by euthanasia and samples; BALF and lung tissue were collected on 23rd day. Further analysis such as total leukocyte count & differential leukocyte cell count, lung histopathology & immunohistochemistry of NF-κB, proteins like Interleukin-1β in BALF and lungs in toxic, treatment groups in comparison with control group were carried out. TAK-242 reduced TLC/DLC values in BALF, including eosinophil, neutrophil, lymphocyte, macrophage counts, lung histological alterations and immunohistochemical positivity of NF-κB and IL-1β proteins expression.