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Patients with recessive dystrophic epidermolysis bullosa (RDEB), a severe form of the inherited blistering skin disorder, have widespread and persistent skin ulcers, and they develop various complications including anaemia, hyperglobulinaemia, hypoalbuminaemia and secondary amyloidosis. These complications are associated with the bioactivities of IL\u20106, and the development of secondary amyloidosis requires the persistent elevation of serum amyloid A (SAA) level. We found that patients with RDEB had significantly higher serum levels of IL\u20106 and SAA compared to healthy volunteers and patients with psoriasis or atopic dermatitis. Both IL\u20106 and SAA were highly expressed in epidermal keratinocytes and dermal fibroblasts of the skin ulcer lesions. Keratinocytes and fibroblasts surrounding the ulcer lesions are continuously exposed to Toll\u2010like receptor (TLR) ligands, pathogen\u2010associated and damage\u2010associated molecular pattern molecules. In\u00a0vitro, TLR ligands induced IL\u20106 expression via NF\u2010\u03baB in normal human epidermal keratinocytes (NHEKs) and dermal fibroblasts (NHDFs). SAA further induced the expression of IL\u20106 via TLR1\/2 and NF\u2010\u03baB in NHEKs and NHDFs. The limitation of this study is that NHEKs and NHDFs were not derived from RDEB patients. These observations suggest that TLR\u2010mediated persistent skin inflammation might increase the risk of IL\u20106\u2010related systemic complications, including RDEB.<\/jats:p>","DOI":"10.1111\/exd.15040","type":"journal-article","created":{"date-parts":[[2024,3,2]],"date-time":"2024-03-02T05:39:42Z","timestamp":1709357982000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Elevated expression of interleukin\u20106 (<scp>IL<\/scp>\u20106) and serum amyloid A (<scp>SAA<\/scp>) in the skin and the serum of recessive dystrophic epidermolysis bullosa: Skin as a possible source of <scp>IL<\/scp>\u20106 through Toll\u2010like receptor ligands and <scp>SAA<\/scp>"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5609-6118","authenticated-orcid":false,"given":"Yoshio","family":"Kawakami","sequence":"first","affiliation":[{"name":"Department of Dermatology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Okayama University  Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ai","family":"Kajita","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Okayama University  Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken\u2010Ichi","family":"Hasui","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Okayama University  Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Matsuda","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Okayama University  Okayama 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