Host Defense Peptide LL-37, in Synergy with Inflammatory Mediator IL-1β, Augments Immune Responses by Multiple Pathways

作者: Jie Yu , Neeloffer Mookherjee , Kathleen Wee , Dawn M. E. Bowdish , Jelena Pistolic

DOI: 10.4049/JIMMUNOL.179.11.7684

关键词:

摘要: The human cathelicidin LL-37 is a cationic host defense peptide and serves as an important component of innate immunity. It has been demonstrated to be multifunctional modulator immune responses, although the mechanism(s) underlying this have not well characterized. In study, it was that synergistically enhanced IL-1β-induced production cytokines (IL-6, IL-10) chemokines such macrophage chemoattractant proteins (MCP-1, MCP-3) in PBMC, indicating role enhancing certain responses. Similarly, chemokine presence GM-CSF, but IFN-γ, IL-4, or IL-12 addition led antagonism, reinforcing specific responses selective restricted particular endogenous mediators. inhibition G protein-coupled receptors PI3K substantially suppressed ability IL-1β enhance MCP-3. Consistent with this, combination activation/phosphorylation kinase Akt transcription factor CREB. NF-κB revealed through demonstration phosphorylation IκBα consequent nuclear translocation subunits p50 p65, antagonistic effects inhibitor phosphorylation. These results together indicate can work synergy inflammatory mediator induction effectors by complex mechanism involving multiple pathways, thus

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