IL-1beta and TNF-alpha induce increased expression of CCL28 by airway epithelial cells via an NFkappaB-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-1beta and TNF-alpha, induced significantly increased expression. Observations from induced sputum and human airway biopsies supported this. Signal transduction studies revealed that IL-1beta and TNF-alpha stimulation induced NFkappaB phosphorylation in A549 cells, but antagonist inhibition of NFkappaB p50-p65 phosphorylation correlated with marked reduction of IL-1beta or TNF-alpha 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 NFkappaB-dependent mechanism.
O'Gorman
Mary T
MT
Mucosal Immunology Laboratory, Institute of Immunology, NUI Maynooth, Co. Kildare, Ireland.
Jatoi
Noor A
NA
Lane
Stephen J
SJ
Mahon
Bernard P
BP
D045744:Cell Line, Tumor; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D019742:Chemokines, CC; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D008168:Lung / Q000166:cytology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D013183:Sputum / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects*
C414047:CCL28 protein, human; D018925:Chemokines; D019742:Chemokines, CC; D007375:Interleukin-1; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha