RAGE-induced asthma: A role for the receptor for advanced glycation end-products in promoting allergic airway disease

Mechanistically, Perkins et al9 demonstrate that reduced responsiveness to effector TH2 cytokines observed in RAGE-deficient mice or after pharmacologic inhibition of RAGE was not due to altered levels of expression of the IL-4/IL-13 receptor components or protein levels of the downstream signaling mediator signal transducer and activator of transcription 6 (STAT6). [...]after a single in vivo pulmonary challenge with rIL-13, comparable levels of activated phosphorylated signal transducer and activator of transcription 6 (pSTAT6) were observed in the lung just after exposure (10 minutes to 1 hour). [...]when primary differentiated human bronchial epithelial cells were stimulated with rIL-13, pSTAT6 was still detected 48 hours later, whereas no pSTAT6 was detected when RAGE was blocked with the FPS-ZM1 antagonist. Because antagonization of key intracellular signaling events associated with asthma pathogenesis would have important therapeutic implications, Perkins et al9 also explored the potential ligands mediating the ability of RAGE signaling to facilitate sustained signaling after TH2 cytokine exposure.