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Toxicarioside H-mediated modulation of the immune microenvironment attenuates ovalbumin-induced allergic airway inflammation by inhibiting NETosis. In the presence of allergens like OVA, neutrophils and other inflammatory cells are recruited, triggering NETosis and the generation of reactive oxygen species (ROS). This process disrupts the balance of immune cells, affecting Th1 and Th2 cells, IL-17 and Treg cells, and memory T cells, thereby promoting allergic asthmatic inflammation. However, ToxH, similar to NEi or NAC, can inhibit NETosis and ROS production, thus modulating the immune environment in allergic asthma and reducing inflammation. [Display omitted] • The novel structural cardiac glycoside, Toxicarioside H (ToxH), effectively inhibits ovalbumin-induced allergic airway inflammation. • ToxH regulates the airway immune microenvironment by maintaining a balance between Th1 and Th2 cells, Th17 and Treg cells, as well as memory T cells. • ToxH mitigates airway inflammation and alters the airway immune microenvironment by suppressing NETosis and reducing ROS production. • Modulating the balance of immune cells in the lung microenvironment with ToxH may represent a promising strategy for treating allergic airway inflammation. Our team identified a new cardiac glycoside, Toxicarioside H (ToxH), in a tropical plant. Previous research has indicated the potential of cardenolides in mitigating inflammation, particularly in the context of NETosis. Therefore, this study sought to examine the potential of ToxH in attenuating allergic airway inflammation by influencing the immune microenvironment. An OVA-induced airway inflammation model was established in BALB/c mice. After the experiment was completed, serum, bronchoalveolar lavage fluid (BALF), and lung tissue samples were collected and further examined using H&E and PAS staining, flow cytometry, immunofluorescence observation, and Western blot analysis. Treatment with ToxH was found to be effective in reducing airway inflammation and mucus production. This was accompanied by an increase in Th1 cytokines (IFN-γ, IL-2, and TNF-β), and the Th17 cytokine IL-17, while levels of Th2 cytokines (IL-4, IL-5, and IL-13) and Treg cytokines (IL-10 and TGF-β1) were decreased in both the bronchoalveolar lavage fluid (BALF) and the CD45+ immune cells in the lungs. Additionally, ToxH inhibited the infiltration of inflammatory cells and decreased the number of pulmonary CD44+ memory T cells, while augmenting the numbers of Th17 and Treg cells. Furthermore, the neutrophil elastase inhibitor GW311616A was observed to suppress airway inflammation and mucus production, as well as alter the secretion of immune Th1, Th2, Th17, and Treg cytokines in the lung CD45+ immune cells. Moreover, our study also demonstrated that treatment with ToxH efficiently inhibited ROS generation, thereby rectifying the dysregulation of immune cells in the immune microenvironment in OVA-induced allergic asthma. Our findings indicate that ToxH could serve as a promising therapeutic intervention for allergic airway inflammation and various other inflammatory disorders. Modulating the balance of Th1/Th2 and Treg/Th17 cells within the pulmonary immune microenvironment may offer an effective strategy for controlling allergic airway inflammation. [ABSTRACT FROM AUTHOR]

• Meloxicam reduced the LPS-induced ROS level in bovine endometrial epithelial cells. • Meloxicam improved the antioxidant capacity of cells challenged by LPS. • Meloxicam inhibited the LPS-induced proinflammatory gene expression. • Meloxicam played an antioxidant role through Nrf2 pathway. • Meloxicam exerted anti-inflammatory effects by inhibiting MyD88/NF-κB pathway. Meloxicam is a selective cyclooxygenase-2 inhibitor and has been widely used in combination with antibiotics to alleviate uterine inflammation and provide analgesia in postpartum cows. Studies have shown that meloxicam has antioxidant and anti-inflammatory effects. However, the link between meloxicam and uterine inflammation and oxidative stress in dairy cows has not been studied. The purpose of this study was to research the effects of meloxicam (0.5 or 5 μM) on oxidative stress and inflammatory response of primary bovine endometrial epithelial cells (BEEC) stimulated by Escherichia coli lipopolysaccharide (1 μg/mL LPS). As a result, LPS stimulated the production of oxidative stress markers and the expression of inflammatory factors, accompanied by a decrease in the activity and the gene transcription of antioxidant enzymes. Co-treatment of meloxicam and LPS reduced the content of oxidative stress markers and the mRNA levels of the pro-inflammatory genes, and improved antioxidant enzyme activities and the corresponding gene expression as compared with the cells treated with LPS alone. Meloxicam attenuated the inhibitory effect of the Nrf2 pathway and the phosphorylation levels of p65 and IκBα caused by LPS. In conclusion, meloxicam alone had no effect on BEEC, but prevented oxidative stress and inflammatory response in LPS-stimulated BEEC. [ABSTRACT FROM AUTHOR]