Lipocalin-2 exacerbates psoriasiform skin inflammation by augmenting T-helper 17 response.

Abstract

Lipocalin-2 (LCN2) is an antimicrobial protein and adipokine associated with insulin resistance, obesity and atherosclerotic disease. Psoriasis is a T-helper (Th)1/Th17-mediated, chronic inflammatory dermatosis related to metabolic syndromes and serum LCN2 levels are elevated in psoriatic patients. We examined the in vivo effects of LCN2 on topical imiquimod (IMQ)-induced psoriasiform skin in BALB/c mice and in vitro on human keratinocytes (KC). Clinically, i.p. injected LCN2 exacerbated erythema and scaling in IMQ-treated murine skin compared with phosphate-buffered saline injection alone, and it augmented interleukin (IL)-17A, IL-17F, IL-22, IL-23p19, IL-12p40, CCL20, tumor necrosis factor-α, chemokine (C-X-C motif) ligand (CXCL)1, CXCL2, DEFB4, DEFB14, LCN2 and S100A7 mRNA levels of IMQ-treated murine skin while it did not increase the mRNA levels of interferon-γ, IL-12p35 or CXCL10. LCN2 in synergy with IL-17 increased mRNA levels of CCL20, LCN2 and DEFB4A but not of CXCL10 in human KC in vitro. These results suggest that LCN2 enhances the expression of Th17 cytokines/chemokines and antimicrobial peptides in murine IMQ-treated psoriatic skin and KC. LCN2 may potentiate the development of psoriasis via the enhancement of Th17- and antimicrobial peptide-mediated inflammation.

• Authors: Carren S Hau, Naoko Kanda, Yayoi Tada, Sayaka Shibata, Hiroshi Uozaki, Toshio Fukusato, Shinichi Sato, Shinichi Watanabe
• Journal: The Journal of dermatology (J Dermatol) Vol. 43 Issue 7 Pg. 785-94 (Jul 2016) ISSN: 1346-8138 [Electronic] England
• PMID: 26702876 (Publication Type: Journal Article)
• Copyright: © 2015 Japanese Dermatological Association.

Chemical References

• Aminoquinolines
• Antimicrobial Cationic Peptides
• CCL20 protein, human
• Chemokine CCL20
• DEFB4A protein, human
• Lipocalin-2
• beta-Defensins
• Imiquimod

Topics

• Aminoquinolines
• Animals
• Antimicrobial Cationic Peptides (metabolism)
• Cells, Cultured
• Chemokine CCL20 (metabolism)
• Female
• Humans
• Imiquimod
• Keratinocytes (metabolism)
• Lipocalin-2 (physiology)
• Mice, Inbred BALB C
• Psoriasis (etiology, pathology)
• Skin (pathology)
• Th1 Cells (metabolism)
• Th17 Cells (metabolism)
• beta-Defensins (metabolism)