Luteolin alleviated neutrophilic asthma by inhibiting IL-36 gamma secretion-mediated MAPK pathways

Context: Luteolin can affect multiple biological functions, such as anti-inflammatory, antioxidant and immune enhancement processes. Luteolin can inhibit inflammation of T2-high asthma, but its role in neutrophilic asthma has been insufficently studied. Objective: This study determines the effect of luteolin on IL-36 gamma secretion-mediated MAPK pathway signalling in neutrophilic asthma. Materials and methods: The asthma model was established by using ovalbumin/lipopolysaccharide (OVA/LPS). Female 6-8-week-old C57BL/6 mice were divided into control, asthma, luteolin (20 mg/kg) and asthma + luteolin (20 mg/kg) groups. To explore the mechanism of anti-inflammatory effects of luteolin in neutrophilic asthma, Beas-2B cells were treated with luteolin (20 mu mol/L), LPS (100 ng/mL), recombinant human IL-36 gamma protein (rhIL-36 gamma; 100 ng/mL) or IL-36 gamma siRNA. Results: IL-36 gamma secretion and MAPK/IL-1 beta signalling were significantly increased in the asthma mouse model compared with the control (p < 0.05). However, the levels of IL-36 gamma secretion and MAPK/IL-1 beta signalling were reduced by luteolin (p < 0.05). In addition, luteolin inhibited IL-36 gamma and MAPK/IL-1 beta levels after LPS (100 ng/mL) stimulation of Beas-2B cells (p < 0.05). We found that in Beas-2B cells, luteolin inhibited activation of the MAPK pathway and IL-1 beta secretion following stimulation with rhIL-36 gamma (100 ng/mL; p < 0.05). Finally, IL-1 beta and phosphorylated MAPK levels were found to be lower in the IL-36 gamma siRNA + LPS (100 ng/mL) group than in the nonspecific control (NC) siRNA + LPS group (p < 0.05). Discussion and conclusions: Luteolin alleviated neutrophilic asthma by inhibiting IL-36 gamma secretion-mediated MAPK pathways. These findings provided a theoretical basis for the application of luteolin in the treatment of neutrophilic asthma.