Table 1: (a) Cathelicidin (LL-37)—the mechanisms of action in psoriasis. (b) S100 proteins—the mechanisms of action in psoriasis. (c) Human β-defensins—the mechanisms of action in psoriasis.
(a)

AMPAbnormalities in psoriasisSource Target cells Receptor Mechanism of action in psoriasis pathohenesis

Cathelicidin (LL-37)(i) Up-regulation
in psoriatic skin
lesions [10, 11]
*Specific processing
of precursor protein;
LL-37 exclusively
detectable form
(ii) Elevated serum level
Mainly keratinocytes
and phagocytes
also T-cells, NK-cells,
monocytes, mast cells
Protein-nucleic acid binding phenomenon on early step of psoriasis pathogenesis
1pDCs TLR-9 Self-DNA-LL-37 complexes activate and prime pDCs for production of INF-α by pDCs [9]
1pDCs TLR-7 Self-RNA-LL-37 complexes activate and prime pDCs for production of INF-α [39]
2mDCs TLR-8 Self-RNA-LL-37 complexes activate and prime mDCs for production of TNF-α, IL-6 and stimulate differentiation of mDCs into mature DCs [39]
   3slanDCsTLR-7, TLR-8, TLR-9Self-RNA-LL-37 complexes activate slanDCs [40]
TLR-7, TLR-8Self-RNA-LL-37 complexes prime slanDCs for production of pro-inflammatory cytokines: TNF-α, IL-6, IL-12p70, IL-12/IL-23p40 through TLR7/8 [40]
   keratinocytes TLR-9 LL-37 enhances TLR-9 expression by keratinocytes and responsiveness to self-DNA with subsequent production of type I IFNs [35]
LL-37 acts synergisitically with IL-17 and IL-22 to prime keratinocytes for production of CXCL-8/IL-8 and IL-6 [36, 42]
MonocytesTLR-independent manner (mediated by ds-DNA)LL-37 transports self-DNA into monocytes leading to the activation of these cells and production of IFN type I [41]
NeutrophilsNADPH oxidase activationPrime neutrophils for production of reactive oxygen species and human alpha-defensins [44]

Monocytes/macrophages, T-cells, neutrophils, mast cells 5FPRL-1LL-37 acts as chemotactic factor [23, 24]
Endothelial cells 5FPRL-1LL-37 promotes neovascularization by induction of the proliferation and migration of endothelial cells and formation of tube-like structures [46]

pDCs: plasmacytoid dendritic cells; 2mDCs: myeloid dendritic cells; 3slanDC: 6-sulfoLacNAc dendritic cells; 4TLRs: toll-like receptors; 5formyl-peptide receptor-like 1 (FPRL-1).
(b)

AMPAbnormalities in psoriasisSource Receptor Target cells Mechanism of action in psoriasis pathohenesis

Psoriasin (S100A7)Up-regulation in psoriatic skin lesions
expression in epidermal suprabasal compartment [13, 59]
Mainly keratinocytes and phagocytes 1RAGE Monocytes,
neutrophils
lymphocytes
Chemoattractant [60]
KeratinocytesAlarmin, prime keratinocytes for enhanced production of pro-inflammatory cytokines: TNF-α, IL-6, IL-8 [62].
NeutrophilsAlarmin, prime neutrophils for production of pro-inflammatory cytokines and chemokines, including: IL-6, IL-8, TNF-α, 2MIP-1α, 3MIP-1β and reactive oxygen species [57]
Endothelial cellsInduction of angiogenesis [63]

Koebnerisin (S100A15) (i) Up-regulation in psoriatic skin lesions
(ii) Expression in epidermal suprabasal compartment, basal keratinocytes, melanocytes, Langerhans cells, dendritic cells, smooth muscle cells and endothelium of blood vessels [14, 59]
Mainly keratinocytes but possibly also other cells 4GiPCR Monocytes,
neutrophils
Chemoattractant [60]
KeratinocytesAlarmin, prime keratinocytes for enhanced production of pro-inflammatory cytokines: TNF-α, IL-6, IL-8 [62].

Calgranulin A/calgranulin B (S100A8/S100A9)Up-regulation in psoriatic skin lesions [70, 71]Phagocytes,
psoriatic keratinocytes, endothelial cells, vascular muscle cells
1RAGE Keratinocytes (i) Alarmin, prime keratinocytes for enhanced production of pro-inflammatory and pro-angiogenic cytokines, such as: IL-6, IL-8, and TNF-α, 5GROs
(ii) Stimulation of proliferation [68, 71]
Immune cells
(monocytes/macrophages, lymphocytes)
Chemoattractant [71]
Endothelial cellsInduction of angiogenesis [71]

Calgranulin C (S100A12)Up-regulation in psoriatic skin lesions [73] 1RAGE

RAGE: multiligand receptor for advanced glycated end products; 2MIP-1α: macrophage inflammatory protein-1α; 3MIP-1β: macrophage inflammatory protein-1β; 4Gi-protein-coupled receptor (GiPCR); 5GROs: growth-related gene product.
(c)

AMPAbnormalities in psoriasisSource Receptor Target cells Mechanism of action in psoriasis pathogenesis

Human β-defensins 1, 2, 3 and 4 (HBD1–4) Up-regulation in psoriatic skin lesions Keratinocytes and phagocytesHBD1–3 1GiPCR Memory T-cells, dendritic cells Chemoattractant [23]
HBD2 1GiPCRNeutrophils mast cells
HBD3-4 1GiPCRMonocytes/macrophages
 HBD2–4 1GiPCR,
2PLC
KeratinocytesAlarmin, prime keratinocytes for enhanced production of pro-inflammatory cytokines and chemokines, including: IL-6, IL-10, 3MCP-1, 4MIP-3α, 5RANTES, 6IP-10 [83]
7EGFR-, 
8STAT1- 
9STAT3-mediated
Stimulate proliferation and migration [83]
HBD2TLR4 Immature dendritic cellsStimulation, induction of Th1-mediated response [86]
HBD3-4TLR-9pDCSActivation and production of IFNs [87]
HBD3-4 10MAPK p38-and 
11ERK1/2-mediated
Mast cells Degranulation of mast cells, production of prostaglandin D2; increase mast cell-mediated vascular permeability in skin [76] production of pruritogenic cytokines-IL-31 [85].

GiPCR: Gi-protein-coupled receptor; 2phospholipase C (PLC); 3MCP-1: monocyte chemoattractant protein-1; 4MIP-3α: macrophage inflammatory protein-3α; 5RANTES: regulated upon activation normal T cell expressed and secreted; 6IP-10: interferon-gamma-inducible protein-10; 7EGFR: epidermal growth factor receptor; 8STAT1: signal transducer and activator of transcription 1; 9STAT3: signal transducer and activator of transcription 3; 10MAPKp38: p38 mitogen-activated protein kinases; 11ERKs; extracellular-signal-regulated kinases.