UBC Theses and Dissertations
Lung epithelial cell responses to host defence peptide Pistolic, Jelena
LL-37, the only cathelicidin family member of cationic host defence peptides in humans, has been shown to mediate multiple immunomodulatory effects and as such is thought to be an important component of innate immune responses. A growing body of evidence suggests that LL-37 affects lung mucosal responses to pathogens through altered regulation of cell migration, proliferation, wound healing, and cell apoptosis. The aforementioned functions are consistent with LL-37 playing a role in regulating lung epithelial inflammatory responses, a role that is, however, not yet clearly defined. The effect of LL-37 on cytokine and chemokine production and signalling regulation in airway epithelial cells were investigated here. In this report I demonstrated that LL-37 induced protein release and transcriptional up-regulation of IL-6 and GRO-a in airway epithelial cells. LL-37 stimulation activated NF-кB signalling, which was further demonstrated herein to robustly regulate production of IL-6 and GRO-a in airway epithelial cells.. With respect to receptor regulation, LL-37-stimulated IL-6 release was demonstrated to be regulated by EGFR and a G-protein coupled receptor, possibly FPRL-1. Furthermore, EGFR was shown to regulate LL-37-stimulated GRO-a. MAP kinase pathways mediated partial signalling regulation of both IL-6 and GRO-a release, while PI3K did not regulate this response. The evidence presented in this report shows that LL-37 is indeed a potent regulator of lung immune responses mediated through activation of multiple signalling pathways.
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