DUOX-Mediated Signaling Is Not Required for LPS-Induced Neutrophilic Response in the Airways.

Abstract

Oxidant production from DUOX1 has been proposed to lead to neutrophil recruitment into the airways when lung homeostasis is compromised. The objective of this study was to determine whether DUOX-derived hydrogen peroxide is required for LPS-induced neutrophil recruitment, using a functional DUOX knock out mouse model. We found that LPS induced profound neutrophilic lung inflammation in both Duoxa(+/+)and Duoxa(-/-) mice between 3h and 24h. Duoxa(-/-) mice had significantly higher neutrophil influx 24h after LPS instillation despite similar cytokine levels (KC, MIP-2, or TGF-α) between the two groups. These findings suggest that LPS-TLR-4-induced KC or MIP-2 cytokine induction and subsequent neutrophil recruitment in the airway does not require DUOX-derived hydrogen peroxide from airway epithelium.