Inhibition of CXCR1 and CXCR2 blocks allergen challenge-induced recruitment of Th2-cells
Next, we examined the role of CXCR1 and CXCR2 on Th2 gene expression and recruitment of Th2 cells. GATA3 is a key transcription factor associated with Th2-mediated allergic lung inflammation4,5. We examined Gata3 mRNA expressions in BALF cells at 28 h post-CDE challenge in CDE-SCM (Fig 1B ) or 28h post-final CDE challenge in CDE-MCM (Fig 1A ). Compared to naïve mice, CDE-challenge in CDE-SCM failed to increase expression levels of Gata3. By contrast, CDE challenge in CDE-MCM sensitized mice induced higher levels ofGata3 mRNA expression compared to naïve mice and mice subjected to CDE-SCM (Fig 2A ). Oral administration of ladarixin in mice subjected to CDE-MCM (Fig 1A right panel ) inhibited CDE challenge-induced increase in Gata3 mRNA expression (Fig 2B ). CDE challenge in CDE-MCM model upregulated expression levels ofIl4, Il5 , Il13 , and Tgfb1 in BALF cells (Fig 2C ), expression levels of Il4 and Il13 in lung tissue (Fig 2D ), and the numbers of IL4, IL5, IL13-secreting and GATA3-expressing Th2-cells in the lungs (Fig 2E ). Oral administration of ladarixin vigorously blocked each of these effects of CDE challenge (Fig 2C-E ), including a remarkable 90% suppression of Il4 mRNA expression (Fig 2C ).