The Pros And Cons Of Antimicrobial Peptides

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Antimicrobial peptides (AMP), also known as host defense peptides (HDPs), exist extensively in all classes of life, contributing not only on immune responses mostly to bacterial infections, also modulating inflammatory response by regulating cytokine, chemotaxis, apoptosis and wound healing. Human HDPs have three major components, namely human α-, β-defensins (HADs and HBDs), and cathelicidin (LL-37). HDPs have a broad spectrum of activity against gram-positive and -negative bacteria, fungal species, and viruses [1-4]. HBDs are small cationic amphipathic peptides with a beta-sheet structure and a signature motif of six cysteines [5]. While LL-37 has its two consecutive leucine residues at the amino-terminal end and 37 amino acids, thus was named accordingly [6].
In addition to the ability of eliminating bacteria similar to antibiotics, HDPs can also naturalize endotoxin produced by gram-negative bacteria, thereby limiting the inflammatory reaction in host [7]. Moreover, with the difference of mechanisms comparing to antibiotics, HDPs will cause less toxicity toward host cells and have a low risk of microbial resistance [8]. HDPs can be induced by various factors. Rather than pathogens, some dietary resources such as fatty acids, histone deacetylase (HDAC) inhibitor, curcumin, vitamin D3, zinc, and disaccharides were reported to have HBD1 and LL37 induction activities, thereby boosting HDPs [3,9-11]. Those results capacitated the therapeutic possibility of HDPs-inducing drug and treatment.
Fatty acids are constructed by a chain of various amount of carbon atoms attached to hydrogen atoms. Fatty acids can be categorized into three groups based on the number of carbon atoms: short-fatty acids (SCFAs) ≤ C5, medium-chain fatty acids (...

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... had a higher induction effect on HBD1 than their counterpart at the same concentration (Figure 3). While on LL-37, 5-phenyl valeric acid (C5), 6-phenyl hexanoic acid (C6) and 7-phenyl heptanic acid (C7) had a higher response than their fatty acids, the peak expression observed at 5-phenyl valeric acid (C5) (Figure 3).
Effects of HDAC inhibitors on HBD1 and LL-37-inducing activities
Histone acetylation and deacetylation are two ways to modify histones on chromosomes, thereby regulating genetic expressions. Butyrate was reported as a non-competitive, reversible histone deacetylases (HDAC) inhibitor [19-21], additionally other HDAC inhibitors, such as sodium valproate, sulforaphane, apcidin etc., were examined as the genetic expression promoters [22-25]. In our study, we determined the effects on HBD1 and LL-37 expression induced by seven HDAC inhibitors (Figure 4).

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