The Expression and Regulation of Chemerin in the Epidermis

Abstract

Chemerin is a protein ligand for the G protein-coupled receptor CMKLR1 and also binds to two atypical heptahelical receptors, CCRL2 and GPR1. Chemerin is a leukocyte attractant, adipokine, and antimicrobial protein. Although chemerin was initially identified as a highly expressed gene in healthy skin keratinocytes that was downregulated during psoriasis, the regulation of chemerin and its receptors in the skin by specific cytokines and microbial factors remains unexplored. Here we show that chemerin, CMKLR1, CCRL2 and GPR1 are expressed in human and mouse epidermis, suggesting that this tissue may be both a source and target for chemerin mediated effects. In human skin cultures, chemerin is significantly downregulated by IL-17 and IL-22, key cytokines implicated in psoriasis, whereas it is upregulated by acute phase cytokines oncostatin M and IL-1β. Moreover, we show that human keratinocytes in vitro and mouse skin in vivo respond to specific microbial signals to regulate expression levels of chemerin and its receptors. Furthermore, in a cutaneous infection model, chemerin is required for maximal bactericidal effects in vivo. Together, our findings reveal previously uncharacterized regulators of chemerin expression in skin and identify a physiologic role for chemerin in skin barrier defense against microbial pathogens.

Senescent fibroblast-derived Chemerin promotes squamous cell carcinoma migration

“…Consistent with this notion, we detected significantly high Chemerin concentrations in senescent dermal fibroblasts in vitro, as well as in the dermal fibroblasts of old healthy individuals and in the stromal fibroblasts of old cSCC patients in situ . This expression pattern was significantly different in the young healthy skin, exhibiting lower Chemerin abundance in the dermis vs. epidermis, as previously demonstrated by Banas et al [56]. Interestingly, in line with a previous publication [57] we found that Chemerin production was significantly decreased in cSCC cells compared to normal keratinocytes.…”

CXCR6-Mediated Simian Immunodeficiency Virus SIVagmSab Entry into Sabaeus African Green Monkey Lymphocytes Implicates Widespread Use of Non-CCR5 Pathways in Natural Host Infections

“…Future studies using knockdown approaches could address this point. It is unlikely that GPR1 and APJ serve as coreceptors for SIVagmSab in PBMC, given the low-level function the we found in transfected cells and limited evidence (in humans and rodents at least) for expression on CD4 ϩ T cells (66)(67)(68)(69)(70). Finally, while we tested all of the major alternative coreceptors that have been reported for various SIVs, it is possible that there are other, as-yet-unidentified seven-transmembrane receptor (7TMR) molecules that could also mediate entry.…”

Antimicrobial and Attractant Roles for Chemerin in the Oral Cavity during Inflammatory Gum Disease

“…qPCR was performed using GoTaq ® qPCR Master Mix (Promega) and primers specific for P. gingivalis proteases (32): rgpA , 5′-TATCCTTCGTGATGTGCGTG-3′, 5′-GCTGTAACGGGAGAAGCAAT-3′; rgpB , 5′-CATTCTCCTCTCTGTTGGGA-3′, 5′-CGTAGGGGATTTGATCAGGA-3′; kgp , 5′-TCAAGCAGT CGATGCAAGC-3′, 5′-ACTTGGGTCAGTTCTTGTCC-3′; and sod , 5′-AATTCCACCACGGTAAGCAC-3′, 5′-TTCTCGATGGACAGTTTGCC-3′; as well as human chemerin 5′-TGGAAGAAACCCGAGTGCAAA-3′, 5′-AGAACTTGGGTCTCTATGGGG-3′, and GAPDH, 5′-GACAGTCAGCCGCATCTTCT-3′, 5′-TTAAAAGCAGCCCTGGTGAC-3′. The relative gene expression normalized to sod (rgpA, rgpB, kgp) and GAPDH (chemerin) was calculated using the 2 −ΔΔCT method (10, 33, 34). …”

“…However, proteases can also inactivate or degrade the attractant and thus limit the extent of chemerin activity (1). Chemerin is broadly expressed in numerous anatomic sites, including liver and fat tissues as well as by epithelial cells in the skin epidermis (7–10), intestinal epithelium (8, 11), and pulmonary airways (8, 12). The strategic positioning of chemerin at the host-environment interface suggests a role in antimicrobial defense.…”