Abstract
There is a growing interest in the complex role of host defense peptides (HDPs) in the pathophysiology of several immune-mediated inflammatory diseases. The physicochemical properties and selective interaction of HDPs with various receptors define their immunomodulatory effects. However, it is quite challenging to understand their function because some HDPs play opposing pro-inflammatory and anti-inflammatory roles, depending on their expression level within the site of inflammation. While it is known that HDPs maintain constitutive host protection against invading microorganisms, the inducible nature of HDPs in various cells and tissues is an important aspect of the molecular events of inflammation. This review outlines the biological functions and emerging roles of HDPs in different inflammatory conditions. We further discuss the current data on the clinical relevance of impaired HDPs expression in inflammation and selected diseases.
Highlights
The human body is in a constant state of conflict with the unseen microbial world that threatens to disrupt the host cell function and colonize the body surfaces
Several studies have shown that host defense peptides (HDPs) may disturb immune tolerance to self-nucleic acids, and in turn significantly enhance cell responses—in particular, plasmacytoid dendritic cells [118]. In the skin, this mechanism has been identified as an important initiator of psoriasis development, where LL-37 and defensins are able to condense self-DNA into particles, which are internalized by pDCs, inducing robust IFN-α response via activation of the Toll-like receptors (TLRs)-9 signaling pathway [119,120]
It has been shown that the phosphorylation of a serine residue of EGFR may modulate the release of beta-defensin 3 (hBD-3) [151], revealingan underlying interdependent relation between the stimulated transforming growth factor β-activated kinase-1 (TAK1), p38α pathway, and phosphorylation of EGFR receptor in the amplified release of hBD-3 in the gastric mucosa involved in H. pylori infection
Summary
The human body is in a constant state of conflict with the unseen microbial world that threatens to disrupt the host cell function and colonize the body surfaces. That being said, expanding our knowledge regarding the molecular mechanisms behind expression, processing, and mutual interactions of HDPs with other immune system components is crucial to better understand inflammation processes, and to develop new methods of anti-inflammatory treatment It is a challenging and long-term task, since a single antimicrobial peptide, e.g., human cathelicidin LL-37, may interact with dozens of proteins/receptors and subsequently engage hundreds of secondary effector proteins, as well as modify expression of >900 genes [6]. The purpose of this review is to evaluate and summarize recent discoveries considering the functional expression and protective attributes of HDPs/AMPs in the acute inflammatory phase and the detrimental effects of their recruitment in chronic inflammation Both in vitro and in vivo studies connecting the underlying mechanisms governing the immunoregulatory role of these peptides in the inflammatory microenvironment will be discussed
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