The human cathelicidin LL-37 — A pore-forming antibacterial peptide and host-cell modulator

Abstract

The human cathelicidin hCAP18/LL-37 has become a paradigm for the pleiotropic roles of peptides in host defence. It has a remarkably wide functional repertoire that includes direct antimicrobial activities against various types of microorganisms, the role of 'alarmin' that helps to orchestrate the immune response to infection, the capacity to locally modulate inflammation both enhancing it to aid in combating infection and limiting it to prevent damage to infected tissues, the promotion of angiogenesis and wound healing, and possibly also the elimination of abnormal cells. LL-37 manages to carry out all its reported activities with a small and simple, amphipathic, helical structure. In this review we consider how different aspects of its primary and secondary structures, as well as its marked tendency to form oligomers under physiological solution conditions and then bind to molecular surfaces as such, explain some of its cytotoxic and immunomodulatory effects. We consider its modes of interaction with bacterial membranes and capacity to act as a pore-forming toxin directed by our organism against bacterial cells, contrasting this with the mode of action of related peptides from other species. We also consider its different membrane-dependent effects on our own cells, which underlie many of its other activities in host defence. This article is part of a Special Issue entitled: Pore-Forming Toxins edited by Mauro Dalla Serra and Franco Gambale.

A parasite-derived 68-mer peptide ameliorates autoimmune disease in murine models of Type 1 diabetes and multiple sclerosis

“…Furthermore, the translation of LL37 to a human immune therapeutic is hampered by its susceptibility to degradation by proteases4748. In contrast, FhHDM-1 is resistant to proteolytic cleavage by human proteases1925, suggesting increased stability and a more attractive pharmacokinetic profile.…”

pH Dependent Antimicrobial Peptides and Proteins, Their Mechanisms of Action and Potential as Therapeutic Agents

“…The most researched of the cationic AMPs reviewed here for potential medical development is LL-37, which is a prospective broad range antimicrobial agent that is also able to induce wound healing and angiogenesis as well as modulate apoptosis [243]. This potential is, however, limited in some cases by the pleiotropic effects of the peptide [244].…”

Peptides: Production, bioactivity, functionality, and applications

“…Several studies have shown that peptides from different sources such as sea hare Turner et al, 1998;Madden et al, 2000;Vaishampayan et al, 2000;Woyke et al, 2001), fish sauce (Thang and Zhao, 2015;Bah et al, 2016), and cod (Xhindoli et al, 2016) were able to block proliferation of carcinogenic cells. However, it seems there is still a long way in order to make commercial use of these potentially potent anticancer peptides to treat different kinds of cancer.…”