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Abstract

The human cathelicidin, LL-37, is a cationic host defence peptide and serves as an essential component of innate immunity. In addition to its modest antimicrobial activity, LL-37 has been demonstrated to be a multifunctional modulator of innate immune responses, although the mechanism(s) of which have not been elucidated. The present study demonstrated that LL-37 could synergistically enhance IL-1β-induced production of cytokines (IL-6, IL-10) and chemokines (MCP-3) in primary human PBMCs. In contrast to the neutralization of LPS-induced secretion of pro-inflammatory cytokines, LL-37 dramatically augmented LPS-stimulated MCP-3 production. LL-37 by itself induced transient phosphorylation of IkB-α. and the subsequent nuclear translocation of NF - kB subunits p50 and p65, which could be further enhanced in the presence of IL-1β. Similar effects of LL-37 and I L-1β were also observed oh activation of Akt and CREB. Therefore, we propose that, in addition to its well-known anti-inflammatory activity, the human host defence peptide LL-37 also plays an important role in boosting the innate immune responses in combination with inflammatory mediator (IL-1β), which provides a new mechanism for LL-37 in modulating the inflammatory responses in innate immunity.