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.
Titanium dioxide (TiO2 ) nanoparticles, widely used for daily products, are believed to be biologically inert, but they may cause adverse effects on cells, presumably depending on the particle size and shape. One of the critical targets of TiO2 particles is epidermal keratinocytes, and their initial response to TiO2 may be production of pro-inflammatory cytokines. We therefore investigated the effects of four types of TiO2 particles on cytokine expression/production by real-time reverse transcription polymerase chain reaction and enzyme-linked immunoassay. The TiO2 particles included three acicular types, FTL-100 (length, 1.68 μm; diameter, 130 nm), FTL-200 (2.86, 210) and FTL-300 (5.15, 270), and one globular type, PT-301 (diameter, 270 nm). Normal human epidermal keratinocytes (NHEK) were cultured with each of the TiO2 particles. During cultivation, the acicular forms of TiO2 were seen by scanning electron microscopy to be internalized by NHEK. The three acicular particles increased the mRNA expressions and supernatant productions of interleukin (IL)-1α, IL-1β, IL-6, tumor necrosis factor-α and IL-8 in particle number-dependent manners, whereas globular PT-301 had very weak activity. Thus, TiO2 particles may induce skin inflammation depending on the size and shape, providing knowledge on their health usage.
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