PMID- 32019242 OWN - NLM STAT- MEDLINE DCOM- 20201117 LR - 20211204 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 21 IP - 3 DP - 2020 Jan 30 TI - Multifaceted Analyses of Epidermal Serine Protease Activity in Patients with Atopic Dermatitis. LID - 10.3390/ijms21030913 [doi] LID - 913 AB - The serine proteases kallikrein-related peptidase (KLK) 5 and KLK7 cleave cell adhesion molecules in the epidermis. Aberrant epidermal serine protease activity is thought to play an important role in the pathogenesis of atopic dermatitis (AD). We collected the stratum corneum (SC) from healthy individuals (n = 46) and AD patients (n = 63) by tape stripping and then measuring the trypsin- and chymotrypsin-like serine protease activity. We also analyzed the p.D386N and p.E420K of SPINK5 variants and loss-of-function mutations of FLG in the AD patients. The serine protease activity in the SC was increased not only in AD lesions but also in non-lesions of AD patients. We found, generally, that there was a positive correlation between the serine protease activity in the SC and the total serum immunoglobulin E (IgE) levels, serum thymus and activation-regulated chemokine (TARC) levels, and peripheral blood eosinophil counts. Moreover, the p.D386N or p.E420K in SPINK5 and FLG mutations were not significantly associated with the SC's serine protease activity. Epidermal serine protease activity was increased even in non-lesions of AD patients. Such activity was found to correlate with a number of biomarkers of AD. Further investigations of serine proteases might provide new treatments and prophylaxis for AD. FAU - Nomura, Hayato AU - Nomura H AD - Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan. FAU - Suganuma, Mutsumi AU - Suganuma M AD - Department of Dermatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. FAU - Takeichi, Takuya AU - Takeichi T AD - Department of Dermatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. FAU - Kono, Michihiro AU - Kono M AD - Department of Dermatology and Plastic Surgery, Akita University Graduate School of Medicine, Hondo 1-1-1, Akita-shi, Akita 010-8543, Japan. FAU - Isokane, Yuki AU - Isokane Y AD - Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan. FAU - Sunagawa, Ko AU - Sunagawa K AD - Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan. FAU - Kobashi, Mina AU - Kobashi M AD - Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan. FAU - Sugihara, Satoru AU - Sugihara S AD - Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan. FAU - Kajita, Ai AU - Kajita A AD - Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan. FAU - Miyake, Tomoko AU - Miyake T AD - Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan. FAU - Hirai, Yoji AU - Hirai Y AD - Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan. FAU - Yamasaki, Osamu AU - Yamasaki O AD - Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan. FAU - Akiyama, Masashi AU - Akiyama M AD - Department of Dermatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. FAU - Morizane, Shin AU - Morizane S AD - Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan. LA - eng GR - 26461658/Grant-in-Aid for Scientific Research (C)/ PT - Journal Article DEP - 20200130 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Biomarkers) RN - 0 (FLG protein, human) RN - 0 (Filaggrin Proteins) RN - 0 (S100 Proteins) RN - 0 (SPINK5 protein, human) RN - 0 (Serine Peptidase Inhibitor Kazal-Type 5) RN - EC 3.4.- (Serine Proteases) SB - IM MH - Adult MH - Biomarkers/*analysis/metabolism MH - Case-Control Studies MH - Dermatitis, Atopic/*enzymology/pathology MH - Epidermis/*enzymology MH - Female MH - Filaggrin Proteins MH - Humans MH - Male MH - Mutation MH - S100 Proteins/genetics/metabolism MH - Serine Peptidase Inhibitor Kazal-Type 5/genetics/metabolism MH - Serine Proteases/*metabolism PMC - PMC7038095 OTO - NOTNLM OT - SPINK5 OT - atopic dermatitis OT - epidermal barrier dysfunction OT - filaggrin OT - kallikrein-related peptidases OT - lympho-epithelial Kazal-type-related inhibitor (LEKTI) OT - serine proteases COIS- The authors declare no conflict of interest. EDAT- 2020/02/06 06:00 MHDA- 2020/11/18 06:00 PMCR- 2020/02/01 CRDT- 2020/02/06 06:00 PHST- 2019/12/18 00:00 [received] PHST- 2020/01/22 00:00 [revised] PHST- 2020/01/28 00:00 [accepted] PHST- 2020/02/06 06:00 [entrez] PHST- 2020/02/06 06:00 [pubmed] PHST- 2020/11/18 06:00 [medline] PHST- 2020/02/01 00:00 [pmc-release] AID - ijms21030913 [pii] AID - ijms-21-00913 [pii] AID - 10.3390/ijms21030913 [doi] PST - epublish SO - Int J Mol Sci. 2020 Jan 30;21(3):913. doi: 10.3390/ijms21030913.