Granulocyte colony-stimulating factor (
G-CSF) has been suggested to be closely associated with neutrophilic
asthma pathogenesis. However, little is known about the factors regulating the production of
G-CSF in neutrophilic
asthma. We previously reported that a
leukotriene B4 receptor 2, BLT2, played an important role in neutrophilic airway
inflammation. Therefore, in the current study, we investigated whether BLT2 plays a role in the production of
G-CSF in
lipopolysaccharide/
ovalbumin (LPS/OVA)-induced
steroid-resistant neutrophilic
asthma. The data showed that BLT2 critically mediated
G-CSF production, contributing to the progression of neutrophilic airway
inflammation. We also observed that
12-lipoxygenase (12-LO), which catalyzes the synthesis of the BLT2
ligand 12(S)-HETE, was also necessary for
G-CSF production. Together, these results suggest that the 12-LO-BLT2-linked signaling network is critical for the production of
G-CSF, contributing to the development of neutrophilic airway
inflammation. Our findings can provide a potential new target for the
therapy of severe neutrophilic
asthma.