Figure 7

Schematic of working mechanism of AR in airway inflammation. The ROS generated by different stimuli including pollens, allergens, growth factors and cytokines are known oxidize membrane lipids to lipid aldehydes such as 4-hydroxynonenal (HNE), which could readily conjugate with glutathione (GSH) and form GS-lipid aldehydes (e.g. GS-HNE). AR reduces GS-HNE to GS-DHN which activates PLC, PKC and PI3K which in turn could lead to activation of transcription factors including NF-κB, AP-1, and STAT-6 that transcribe various inflammatory genes. The inflammatory markers propagate the signals in autocrine and/or paracrine fashion and cause airway inflammation and asthma pathogenesis. AR inhibition blocks this cascade upstream of various kinases and thus prevents inflammation.