{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:59:33Z","timestamp":1791248373887,"version":"4.1.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2014,11,1]],"date-time":"2014-11-01T00:00:00Z","timestamp":1414800000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Several dermatoses, including psoriasis, atopic dermatitis, and rosacea, alter the expression of the innate immune effector human cathelicidin antimicrobial peptide (CAMP). To elucidate the roles of aberrant CAMP in dermatoses, we performed cDNA array analysis in CAMP-stimulated human epidermal keratinocytes, the primary cells responding to innate immune stimuli and a major source of CAMP LL37 in skin. Among LL37-inducible genes, IL-1 cluster genes, particularly IL36G, are of interest because we observed coordinate increases in CAMP and IL-36\u03b3 in the lesional skin of psoriasis, whereas virtually no CAMP or IL-36\u03b3 was observed in nonlesional skin and normal skin. The production and release of IL-36\u03b3 were up to 20\u201330 ng\/ml in differentiated keratinocytes cultured in high-calcium media. G-protein inhibitor pertussis toxin and p38 inhibitor suppressed IL-36\u03b3 induction by LL37. As an alarmin, LL37 induces chemokines, including CXCL1, CXCL8\/IL8, CXCL10\/IP-10, and CCL20\/MIP3a, and IL-36 (10\u2013100 ng\/ml) augments the production of these chemokines by LL37. Pretreatment with small interfering RNA against IL36\u03b3 and IL-36R IL36R\/IL1RL2 and IL1RAP suppressed LL37-dependent IL8, CXCL1, CXCL10\/IP10, and CCL20 production in keratinocytes, suggesting that the alarmin function of LL37 was partially dependent on IL-36\u03b3 and its receptors. Counting on CAMP induction in innate stimuli, such as in infection and wounding, IL-36\u03b3 induction by cathelicidin would explain the mechanism of initiation of skin inflammation and occasional exacerbations of psoriasis and skin diseases by general infection.<\/jats:p>","DOI":"10.4049\/jimmunol.1302574","type":"journal-article","created":{"date-parts":[[2014,10,11]],"date-time":"2014-10-11T04:13:50Z","timestamp":1413000830000},"page":"5140-5148","source":"Crossref","is-referenced-by-count":140,"title":["Alarmin Function of Cathelicidin Antimicrobial Peptide LL37 through IL-36\u03b3 Induction in Human Epidermal Keratinocytes"],"prefix":"10.1093","volume":"193","author":[{"given":"Na","family":"Li","sequence":"first","affiliation":[{"name":"Department of Dermatology, Graduate School of Medicine, Tohoku University , Sendai, Miyagi 980-8574 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenshi","family":"Yamasaki","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Graduate School of Medicine, Tohoku University , Sendai, Miyagi 980-8574 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rumiko","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Graduate School of Medicine, Tohoku University , Sendai, Miyagi 980-8574 ,","place":["Japan"]},{"name":"Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University , Sendai, Miyagi 980-8574 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sawako","family":"Fukushi-Takahashi","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Graduate School of Medicine, Tohoku University , Sendai, Miyagi 980-8574 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryoko","family":"Shimada-Omori","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Graduate School of Medicine, Tohoku University , Sendai, Miyagi 980-8574 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Asano","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Graduate School of Medicine, Tohoku University , Sendai, Miyagi 980-8574 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Setsuya","family":"Aiba","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Graduate School of Medicine, Tohoku University , Sendai, Miyagi 980-8574 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,11,15]]},"reference":[{"key":"2025030707445826600_r1","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1111\/j.1365-2567.2006.02399.x","article-title":"Control of the innate epithelial antimicrobial response is cell-type specific and dependent on relevant microenvironmental stimuli","volume":"118","author":"Schauber","year":"2006","journal-title":"Immunology"},{"key":"2025030707445826600_r2","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1111\/j.0022-202X.2005.23713.x","article-title":"Anti-fungal activity of cathelicidins and their potential role in Candida albicans skin infection","volume":"125","author":"L\u00f3pez-Garc\u00eda","year":"2005","journal-title":"J. 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