Calcipotriol Increases hCAP18 mRNA Expression but Inhibits Extracellular LL37 Peptide Production in IL-17/IL-22-stimulated Normal Human Epidermal Keratinocytes

Abstract

Interleukins (IL)-17A and -22 are involved in the patho-genesis of psoriasis. Cathelicidin LL37 serves as not only antimicrobial peptide but also as autoinflammatory mediator. 1,25-Dihydroxyvitamin D3 analogues, such as calcipotriol, are used as topical treatment for psoriasis. However, the effect of calcipotriol on the mRNA expression/production of human cathelicidin antimicrobial protein (hCAP18) and LL37 peptide by IL-17A/IL-22-stimulated keratinocytes remains controversial. To evaluate the modulatory action of calcipotriol on the production of hCAP18 and LL37, we analysed hCAP18 mRNA expression and hCAP18/LL37 peptide production in IL-17A/IL-22-stimulated cultured human keratinocytes by real-time qPCR, ELISA, western blotting, and immunocytostaining. By western blotting, hCAP18 protein was detected in keratinocytes cultured for 72 h with IL-17/IL-22. Calcipotriol increased hCAP18 mRNA expression in IL-17/IL-22-stimulated keratinocytes. However, LL37 peptide in the culture supernatants was reduced by calcipotriol. Immunostaining revealed that the overproduced LL37 resides within the cells. LL37 promotes psoriasis via interaction with extracellular DNA, but may suppress psoriasis by interfering cytosolic DNA.

IL-22/STAT3-Induced Increases in SLURP1 Expression within Psoriatic Lesions Exerts Antimicrobial Effects against Staphylococcus aureus

“…IL-22 induces production of various AMPs, including β-defensin2, S100A7 and LL37, in regions of skin inflammation [ 23 , 24 ]. Because it has been reported that prostate and testis expressed protein (PATE), which is a secreted protein containing a Ly6 domain, has antibacterial activity [ 29 ], we investigated the antibacterial activity of partially purified rhSLURP1 secreted from SLURP1-transfected RK13 cells.…”

“…IL-22-induced AMPs such as β-defensin2, S100A7 and CAP18/LL37 all have the ability to suppress growth of S . aureus [ 23 , 24 ].…”

Natural killer cells in inflammatory heart disease

“…We and others have reported NK cells to be protective against both coxsackievirus B (CBV) and murine cytomegalovirus (MCMV)-induced myocarditis, albeit these studies depleted both NK and NKT populations simultaneously [90, 91]. The direct mediators of viral recognition are unknown in CBV and MCMV, though ligation of the activating receptor Ly49H by the viral glycoprotein m157 and destabilization of inhibitory receptor Ly49C by abnormal MHCI expression is necessary in limiting MCMV infection [92, 93]. …”

The Vitamin D3 analogue calcipotriol suppresses CpG-activated TLR9-MyD88 signalling in murine plasmacytoid dendritic cells

“…Vitamin D3 analogues are widely used to treat psoriasis, and the mechanisms underlying their therapeutic effectiveness have been studied mainly in keratinocytes, T cells and conventional DCs . pDCs play a triggering role in psoriatic lesions, but it is not known whether or how vitamin D3 analogues affect pDCs.…”