Epidermicin NI01 and human β-defensin 2 as modulators of macrophage subset responses

Antimicrobial peptides (AMPs) and host defence peptides (HDPs) have been extensively investigated for their antimicrobial activity and evidence suggests that they can also modulate the host immune system. However, little is known about their effects on macrophages, a key cell population in inflammatory responses that mediates communication between innate and adaptive immunity. Macrophages are a pleiotropic cell population composed of different subsets that orchestrate diverse stages of inflammation with roles ranging from pro- to anti-inflammatory and thus, targets for immunomodulation in different diseases. Here, THP-1-derived M1- and M2-like cells (pro- and anti-inflammatory respectively) under stimulation of TLR4 by LPS were used as a model to investigate potential immunomodulatory effects of these peptides on macrophages. Human β-defensin 2 in the presence of the TLR4 agonist K12 LPS, up-regulated the release of the pro-inflammatory cytokines TNFα and IL-1β from M1- and M2-like macrophages. Conversely, epidermicin NI01 strongly up-regulated release of a number of pro-inflammatory cytokines in the presence and absence of K12 LPS in M1-like cells but only a subset of those in M2-like cells. Various inhibitors of pro-inflammatory cytokine release pathways allowed us to partially elucidate the mechanisms via which this happens. Regulation of macrophage function by these and other peptides may have clinical implications in a wide range of immune-related disorders, but there is much we do not yet understand about what role, if any, epidermicin may have in these processes. Human β-defensin 2-induced upregulation of TNFα and IL-1β from M2-like cells might be important in conditions driven by sustained M2 anti-inflammatory factors such as fibrosis.

Author dc:creator

• Durante, Barbara

Contributors dc:contributor

• Andrew Foey, Mathew Upton

• Antimicrobial peptides
• Macrophages
• M1
• M2
• TNF alpha

Language dc:language

eng

Identifier

10026.1/16218

OAI identifier oai:identifier

oai:pearl.plymouth.ac.uk:foh-theses-other-1213