Correlation between oxidative stress and the NF-κB signaling pathway in the pulmonary tissues of obese asthmatic mice

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Abstract
The obesity‑asthma phenotype is characterized by increased asthma severity and decreased glucocorticoid responsiveness. To date, the mechanism underlying the association between obesity and asthma remain to be fully elucidated. The present study investigated the correlation between oxidative stress and the nuclear factor (NF)‑κB pathway in obese asthmatic mice. The animals were divided into the following groups: Control (n=8), comprising C57BL/6J mice without exposure to a high‑fat diet; non‑obese asthma group (n=8), comprising mice of a normal weight subjected to the induction of asthma; obese control group (n=8), comprising C57BL/6J mice subjected to a high‑fat diet; and obese asthmatic group (n=8), comprising obese mice subject to the induction of asthma. The levels of the malondialdehyde (MDA) oxidant and glutathione (GSH) antioxidant in the lungs and bronchoalveolar lavage fluid (BALF) were measured using ELISA. The expression levels of inhibitory κB kinase‑β (IKK‑β) and the inhibitor of κBα (IκB‑α) in the pulmonary tissues was determined using western blot analysis. An electrophoretic mobility shift assay was performed to determine the transcription activity of NF‑κB. The levels of MDA in the BALF and lung tissues increased significantly in the two asthmatic groups, compared with the control groups (P<0.01). The asthmatic mice showed significantly lower concentrations of GSH in the BALF and lung tissues, compared with the control groups (P<0.01). In the asthmatic animals, the expression of IκB kinase (IKK)‑β and activation of NF‑κB were upregulated in the pulmonary tissues, compared with those in the control groups (P<0.01). The expression of IKK‑β and transcriptional activity of NF‑κB were significantly higher the in obese asthmatic mice, compared with the non‑obese asthmatic mice (P<0.01). On examining the expression levels of IκB‑α in the pulmonary tissues, a significant reduction was found in the asthmatic animals, compared with the controls (P<0.01). In addition, the level of IκB‑α was significantly lower in the obese asthmatics, compared with the non‑obese asthmatics (P<0.01). MDA was positively correlated with NF‑κB in the obese asthmatic group (R=0.83; P<0.05) and non‑obese asthmatic group (R=0.82; P<0.05). Oxidative stress was upregulated in the pulmonary tissues of the asthmatic mice. This upregulation was more marked in the obese asthmatic mice, and was positively correlated with activation of the NF‑κB signaling pathway in the pulmonary tissues. The results in the present study indicated that higher oxidative stress and activation of the NF‑κB signaling pathway were observed in the lung tissues of the obese asthmatics. Furthermore, a positive correlation was identified between oxidative stress and NF‑κB.

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