Antimicrobial peptides in the pathogenesis of psoriasis

Abstract

One characteristic abnormality of lesional skin in psoriasis is the excessive production of antimicrobial peptides and proteins (AMPs). AMPs typically are small (12-50 amino acids), have positive charge and amphipathic structure, and are found in all living organisms including mammals, insects, plants and invertebrates. These peptides are best known for their integral role in killing pathogenic microorganisms; however, in vertebrates, they are also capable of modifying host inflammatory responses by a variety of mechanisms. In psoriatic lesions, many AMPs are highly expressed, and especially the associations between psoriasis and cathelicidin, b-defensins or S100 proteins have been well studied. Among them, a cathelicidin peptide, LL-37, has been highlighted as a modulator of psoriasis development in recent years. AMPs had been thought to worsen psoriatic lesions but recent evidence has also suggested the possibility that the induction of AMPs expression might improve aspects of the disease. Further investigations are needed to uncover a previously underappreciated role for AMPs in modulating the immune response in psoriasis, and to improve disease without the risks of systemic immunosuppressive approaches.

Interplay between CXCR2 and BLT1 Facilitates Neutrophil Infiltration and Resultant Keratinocyte Activation in a Murine Model of Imiquimod-Induced Psoriasis

“…In agreement with this, CXCR2 density is elevated on neutrophils from psoriatic individuals compared with those from healthy volunteers (35), along with increased IL-8 and CXCL1 levels in psoriatic epidermis (29). Furthermore, cathelicidin antimicrobial peptide (also known as LL-37), another potential ligand for CXCR2 (36), is overexpressed in human psoriatic keratinocytes and has been suggested to play a role in the pathogenesis of inflammatory skin diseases including psoriasis (37,38). Much to our interest, cathelicidin triggers LTB 4 synthesis from human neutrophils (39), as well as CXCL1 and CXCL2, as shown in Fig.…”

Effects of linear amphiphilicity on membrane interactions of C-terminal thrombin peptides

“…Antimicrobial peptides (AMPs) constitute one such class of potential anti-infective drugs, and are currently receiving much attention in both academic research and drug development (3)(4)(5)(6)(7)(8).…”

CD1b-autoreactive T cells contribute to hyperlipidemia-induced skin inflammation in mice

“…In fact, anti-TNF is a mainstay of therapy for psoriasis, and anti-IL-17A therapy was recently approved as a first-line systemic treatment (10,11). While the involvement of peptide-reactive T cells has been well defined (12)(13)(14)(15), the role of lipid-reactive T cells in psoriasis remains largely unknown. Since psoriasis and cardiovascular disease are correlated with hyperlipidemia and recent studies have identified CD1-restricted self-lipid-reactive T cells in the blood or skin of humans (16)(17)(18)(19), we developed a new mouse model for the study of human CD1-restricted T cell responses to self-lipids in vivo.…”