Lipocalin 2 Participates in the Epidermal Differentiation and Inflammatory Processes of Psoriasis

Abstract

As a multifunctional cytokine, lipocalin 2 is weakly expressed in skin and serum under normal conditions. However, it is over-expressed by neutrophils and keratinocytes in the skin lesions and sera in several skin diseases. Recent studies demonstrated that lipocalin 2 participates in the pathogenesis of psoriasis by exerting versatile effects on skin resident cells and infiltrating immune cells. Lipocalin 2 inhibits the synthesis of keratin, involucrin, and loricrin in keratinocytes, leading to epidermal parakeratosis via the Tcf7l1-lipocalin 2 signaling axis. It also recruits inflammatory cells such as T cells and neutrophils into skin lesions via the IL-23/IL17, p38-MAPK, and ERK-1/2 signaling pathways. Additionally, lipocalin 2 and other cytokines such as IL-17 have the synergetic effects on skin cells. The neutralization of lipocalin 2 or relevant cytokines can alleviate psoriasis, verifying that lipocalin 2 is an effective interfering target for psoriasis. In this review, we summarize the roles of lipocalin 2 in the processes of psoriatic inflammation and the promising therapeutic strategies based on lipocalin 2-related molecules.

Consequences of Autophagy Deletion on the Age-Related Changes in the Epidermal Lipidome of Mice

“…Several of the other lipid-related DEG induced in the autophagy-deficient keratinocytes were pro-inflammatory genes, several of them involved in neutrophil chemotaxis. These were the cyto- and chemokines interleukin 24 (IL24) and C-X-C motif ligand 3 (CXCL3), adipose glutathione S transferase (GSTA4), and lipocalin 2 (LCN2), as well as prostaglandin E synthase (PTGES), the products of the latter regulating neutrophil function [ 23 , 24 , 25 ]. Among them, PTGES and CXCL3 (only by trend) expression increased in autophagy-deficient groups compared with the autophagy-competent groups.…”

Overexpression of Plakophilin2 Mitigates Capillary Leak Syndrome in Severe Acute Pancreatitis by Activating the p38/MAPK Signaling Pathway

“…Dysiarenone blocks the anti-inflammatory effects of the NF-κB signaling pathway by impeding the phosphorylation of p65 and p38 in LPS-stimulated RAW 264.7 macrophages. 48 According to Xia et al, 49 activation of the p38/MAPK signaling pathway might attract inflammatory cells, such as T cells and neutrophils. Conversely, suppressing p38 phosphorylation helps relieve chronic inflammatory illnesses.…”

Significance of Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) for the Monitoring of Treatment Response to Cyclosporine in Patients with Psoriasis

“…Although NGAL was primarily identified in granules of neutrophils, its expression was previously found to be increased in skin areas associated with disturbed keratinocyte differentiation regardless of the underlying condition [ 7 , 17 ]. It belongs to antimicrobial peptides and expression of NGAL in normal epidermis is low, but a significant enhancement of its expression may occur in different inflammatory skin disorders including psoriasis [ 1 , 8 ]. The molecule may participate in the pathogenesis of psoriasis primarily via the activation of neutrophils [ 1 ] and the enhancement of T-helper (Th)1/Th17-mediated inflammation [ 2 ].…”

“…However, the production of NGAL was found to be augmented by IL-1β, IL-17 and TNF-α [ 18 ]. NGAL does not only recruit T cells and neutrophils into skin lesions, but also promotes epidermal parakeratosis [ 8 ].…”

“…Both NGAL and PCSK9 can be produced by keratinocytes [ 1 , 5 ]. Their tissue expression was shown to be enhanced within the lesioned skin in psoriasis [ 4 , 5 , 6 , 7 ] and their serum levels were increased in psoriatic patients [ 3 , 8 ]. A decrease in tissue NGAL expression was previously observed after biologics (risankizumab, ustekinumab) [ 9 ] and the narrow-band UVB phototherapy (nb-UVB) [ 10 ].…”