Human airway trypsin-like protease (HAT), a novel serine protease in the airways, enhances cell growth and IL-8 production. The expression and role of HAT in the skin however, is unknown. Immunofluorescence staining and reverse transcription (RT)-PCR were done to know HAT production in normal and psoriatic tissues and keratinocyte cell lines. Cell growth and/or IL-8 release analyses were made by bromo-deoxyuridine (BrdU) uptake and ELISA. Psoriatic epidermis showed more extensive immunofluorescence expression of HAT, and less extensive expression of protease-activated receptor (PAR)-2. RT-PCR demonstrated a higher HAT and a lesser PAR-2 mRNA expressions in psoriatic epidermis. Normal keratinocyte and epidermoid carcinoma cell lines expressed HAT and PAR-2 mRNA, and immortalized keratinocytes (HaCaT) expressed PAR-2, but not HAT mRNA. PAR-2 was detected along the keratinocyte surface in culture and became invisible upon HAT stimulation, suggesting a process of its internalization. HAT or PAR-2 activating peptide did not enhance BrdU uptake, but induced an IL-8 release. Treatment with HAT and IL-1beta synergistically increased the effect of IL-8 release. Inhibition of PAR-2 resulted in a decreased HAT-induced IL-8 release. Thus, HAT might promote PAR-2-mediated IL-8 production to accumulate inflammatory cells in the epidermal layer of psoriasis.

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Background The aim of this study is to investigate the efficacy of on-demand therapy with 20-mg Vonoprazan (VPZ) as a maintenance therapy for patients with mild RE. Methods On-demand therapy of orally taking one 20-mg tablet of VPZ only when reflux symptoms occurred was carried out in 30 patients with mild RE who were in a state of endoscopic remission on maintenance therapy using PPI and answered ‘very satisfied’ or ‘satisfied’ to an overall satisfaction survey. Patients who were remission on 24 weeks after the initiation of on-demand therapy continued the on-demand therapy for a total of 48 weeks. RE symptoms were assessed at 24 and 48 weeks after the initiation of on-demand therapy. Patient satisfaction, symptoms (F-scale), and gastrin level before breakfast were compared before and after the on-demand therapy. In addition, the number of VPZ tablets taken and the frequency (regular, temporary, rare) of its administration were examined. Results One of the 30 patients dropped out of on-demand therapy 1 week after its initiation. At the 24-week follow-up, recurrence of RE was found in 13.8% of the patients. There were no significant differences in the level of the F-scale score, overall level of satisfaction, and gastrin level before and after the on-demand therapy. During the 24-week on-demand therapy, patients took 33 (median) VPZ tablets. 31.0% of the patients took VPZ on a regular basis (at least 2 tablets a week); the remaining patients took VPZ on a temporary or rare basis. After additional 24 weeks, 21 of 25 patients who maintained remission completed the 48-week study. 15.4% had recurrent disease (grade A and B). There were no significant differences in the F-scale score, overall level of satisfaction, and gastrin level before and 48 weeks after the on-demand therapy. At the end of the 48-week on-demand therapy, patients had taken 69 VPZ tablets, and 42.9% of the patients took VPZ on a regular basis. Conclusion Discussion: On-demand therapy with 20-mg VPZ is an effective alternative for PPI maintenance therapy for mild RE. Disclosure All authors have declared no conflicts of interest.