Prevention of redox signaling by AR inhibition.

<p>Stimulation with Ragweed pollens, allergens, growth factors, or cytokines cause increased ROS production inside the cells. The ROS could oxidize membrane lipids to form lipid aldehydes such as 4-hydroxynonenal (HNE), which readily reacts with glutathione and form GS-conjugates such as GS-HNE. AR catalyzes the reduction of GS-HNE into GS-DHN. The latter is known to activate various downstream protein kinases such as PKC, PI3K and MAPK activating transcription factors NF-κB and AP-1 which transcribe various inflammatory markers, including IL-13 which in paracrine fashion induces more ROS formation. The GS-DHN could also phosphorylate JAK-1 and MAPK such as ERK1/2, eventually phosphorylating and activating STAT-6 which translocate to the nucleus and transcribe genes including mucin genes leading to goblet cell metaplasia. The continuously formed GSDHN may amplify the signaling loop by increased ROS production via PKC/NOX pathway. Inhibition of AR blocks the initial as well as the amplification loop and prevents ROS-induced pathological changes <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0014440#pone.0014440-Ramana1" target="_blank">[Ref. 31]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0014440#pone.0014440-Tammali1" target="_blank">[32]</a>.