IL-1β and TNF-α induce increased expression of CCL28 by airway epithelial cells via an NFκB-dependent pathway

CCL28 is a mucosal chemokine that attracts eosinophils and T cells via the receptors CCR3 and CCR10. Consequently, it is a candidate mediator of the pathology associated with asthma. This study examined constitutive and induced expression of CCL28 by A549 human airway epithelial-like cells. Real-time RT-PCR and ELISA of cultured cells and supernatants revealed constitutive levels of CCL28 expression to be low, whereas IL-1β and TNF-α, induced significantly increased expression. Observations from induced sputum and human airway biopsies supported this. Signal transduction studies revealed that IL-1β and TNF-α stimulation induced NFκB phosphorylation in A549 cells, but antagonist inhibition of NFκB p50-p65 phosphorylation correlated with marked reduction of IL-1β or TNF-α induced CCL28 expression. Together these studies imply a role for CCL28 in the orchestration of airway inflammation, and suggest that CCL28 is one link between microbial insult and the exacerbation of pathologies such as asthma, through an NFκB-dependent mechanism.