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Review
, 55 (2), 75-85

Therapeutic Effects of Synthetic Antimicrobial Peptides, TRAIL and NRP1 Blocking Peptides in Psoriatic Keratinocytes

Affiliations
Review

Therapeutic Effects of Synthetic Antimicrobial Peptides, TRAIL and NRP1 Blocking Peptides in Psoriatic Keratinocytes

Sunhyo Ryu et al. Chonnam Med J.

Abstract

Psoriasis is a chronic, recurrent, heterogeneous, cutaneous inflammatory skin disease for which there is no cure. It affects approximately 7.5 million people in the United States. Currently, several biologic agents that target different molecules implicated in the pathogenic processes of psoriasis are being assessed in diverse clinical studies. However, relapse usually occurs within weeks or months, meaning there is currently no cure for psoriasis. Therefore, recent studies have discovered diverse new potential treatments for psoriasis: inhibitors of bacteria such as Staphylococcus aureus, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and neuropilin 1 (NRP1). A promising approach that has recently been described involves modifying antimicrobial peptides to develop new cutaneous anti-bacterial agents that target inflammatory skin disease induced by Staphylococcus. Increased expression of TRAIL and its death receptors DR4 and DR5 has been implicated in the pathogenesis of plaque psoriasis. In addition, TRAIL has the ability to inhibit angiogenesis by inducing endothelial cell death and by negative regulation of VEGF-induced angiogenesis via caspase-8-mediated enzymatic and non-enzymatic functions. Since NRP1 regulates angiogenesis induced by multiple signals, including VEGF, ECM and semaphorins, and also initiates proliferation of keratinocytes through NF-κB signaling pathway in involved psoriatic skin, targeting NRP1 pathways may offer numerous windows for intervention in psoriasis. In this review, we will focus on the current knowledge about the emerging role of synthetic antimicrobial peptides, TRAIL and NRP1 blocking peptides in the pathogenesis and treatment of psoriasis.

Keywords: Anti-Bacterial Agents; Neuropilin-1; Psoriasis; TNF-Related Apoptosis-Inducing Ligand.

Conflict of interest statement

CONFLICT OF INTEREST STATEMENT: None declared.

Figures

FIG. 1
FIG. 1. The pathogenesis of psoriasis. Aberrant interplay of keratinocytes and immune cells in psoriasis. Cytokines produced by immune cells act on keratinocytes to activate further inflammatory mediator such as cytokines, chemokines, VEGF and AMPs, which creates an inflammatory loop.
FIG. 2
FIG. 2. Schematic diagram of a synthetic antimicrobial peptides on antimicrobial and anti-inflammatory activity in psoriatic keratinocytes. The antimicrobial and anti-inflammatory activity of the synthetic antimicrobial peptides (AMPs) may be attributed to: (I) a direct antimicrobial activity against S. aureus, (II) the ability of synthetic AMPs to bind bacterial factors such as peptidoglycan (PGN), lipoteichoic acid (LTA), protein A, α-Toxin and superantigens (SAg), (III) the inhibitory activity of synthetic AMPs on the keratinocytes secretion of proinflammatory cytokines, chemokines, endogenous AMPs and VEGF.
FIG. 3
FIG. 3. TRAIL and TRAIL receptors.
FIG. 4
FIG. 4. Structure of the neuropilins (NRPs). (A) The transmembrane and soluble forms of both NRPs. (B) The NRP1 and the NRP2 splice variants (NRP2a and NRP2b).

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