Chemokine-Derived Peptides: Novel Antimicrobial and Antineoplasic Agents

Abstract

Chemokines are a burgeoning family of chemotactic cytokines displaying a broad array of functions such as regulation of homeostatic leukocyte traffic and development, as well as activating the innate immune system. Their role in controlling early and late inflammatory stages is now well recognized. An improper balance either in chemokine synthesis or chemokine receptor expression contributes to various pathological disorders making chemokines and their receptors a useful therapeutic target. Research in this area is progressing rapidly, and development of novel agents based on chemokine/chemokine receptors antagonist functions are emerging as attractive alternative drugs. Some of these novel agents include generation of chemokine-derived peptides (CDP) with potential agonist and antagonist effects on inflammation, cancer and against bacterial infections. CDP have been generated mainly from N- and C-terminus chemokine sequences with subsequent modifications such as truncations or elongations. In this review, we present a glimpse of the different pharmacological actions reported for CDP and our current understanding regarding the potential use of CDP alone or as part of the novel therapies proposed in the treatment of microbial infections and cancer.

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

“…In addition to their pH dependent antimicrobial activity, both myt C and myt Cc possessed chemotactic activity and appeared to be the first chemokine/cytokine-like molecules identified in bivalves [59,202]. These results added to the increasing evidence that AMPs can serve as cytokines [90,203] and interestingly, it is also becoming clear that these latter peptides are able to exhibit antimicrobial activity [204,205] that is enhanced by low pH [206,207]. Molluscs are also a source of histidine containing AMPs with pH dependent activity, such as the peptide, KPS-1, which was isolated from, Atrina pectinate , and under acid conditions, inhibited the growth of a range of Gram-negative bacteria, including P. Aeruginosa , S. typhimurium and Enterobacter sakazakii [60].…”

The Rising Role of Mesenchymal Stem Cells in the Treatment of Various Infectious Complications

“…MSCs have been shown to exhibit the following antimicrobial properties: (1) capacity to enhance antibacterial activity by interaction with the host innate immune system in order to increase antibiotic sensitivity, increase bacterial killing, and slow bacterial growth; (2) capacity to enhance bacterial clearance in preclinical models of sepsis, cystic fibrosis, and ARDS; and (3) secretion of antimicrobial peptides such as: interleukin (IL)-17, indoleamine 2,3-dioxygenase (IDO), β-defensins, lipocalin-2, and cathelicidin LL-37 [44][45][46]. Members of the chemokine family have been found to have antimicrobial peptide activity although the role of chemokines in immunity during infection is rather complicated [47].…”

Antimicrobial Peptides and Cancer: Potential Use of Antimicrobial-Like Peptides in Chemotherapy

“…The AMPs induce pores and/or channels in the cell membrane for cell entry; however, they also can recruit chemokines and their receptors (i.e. CCR6) to assist in their function [4]. In fact, the AMPs themselves have been referred to a "mini-chemokine ligands".…”

“…The AMPs demonstrate the potential to function as novel cancer therapeutic agents due to their ability to lyse and destabilize biomembranes, interact and/or form transmembrane channels, and engage in modulating host immunity against foreign invasive agents [3]. AMPs are known to act in concert with chemokine activities, histamine release, and angiogenesis regulation [4]. The objective of the present review is to provide evidence that AMPs could serve as ideal candidates for cancer chemotherapy.…”