{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T15:44:46Z","timestamp":1784907886122,"version":"3.55.0"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2011,11,1]],"date-time":"2011-11-01T00:00:00Z","timestamp":1320105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,11,1]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>Background Prurigo nodularis (PN) is a chronic dermatitis characterized by discrete, raised, and firm papulonodules with intense pruritus. The pathogenesis still remains to be elucidated.<\/jats:p>\n                  <jats:p>Objectives To clarify the role of Th1 and Th2 cytokines in the pathogenesis of PN.<\/jats:p>\n                  <jats:p>Methods We examined the cytokine signatures, such as phosphorylation of STAT1, STAT3 and STAT6, HLA-DR and hyaluronan accumulation, to reveal the Th1 and Th2 cytokine influence on the lesional epidermis of PN.<\/jats:p>\n                  <jats:p>Results We first optimized antigen retrieval methods to detect these signatures with antibodies for phospho-STAT1 (pSTAT1), phospho-STAT3 (pSTAT3), phospho-STAT6 (pSTAT6), HLA-DR and hyaluronic acid binding protein (HABP) on the formalin-fixed paraffin-embedded sections of psoriasis, lichen planus and atopic dermatitis biopsy samples. Activation of STAT1 and STAT6 in epidermis by Th1 and Th2 cytokines was further confirmed in a cultured skin equivalent model treated with interferon-\u03b3 or interleukin (IL)-4\/IL-13. With the relevant immunostaining methods, we examined the cytokine signatures in 22 cases of PN. The results revealed that (i) the entire epidermis of 19 cases was stained with anti-pSTAT6 antibody, (ii) 21 cases demonstrated nuclear staining with anti-pSTAT3 antibody, (iii) the entire epidermis of 21 cases was stained with HABP, (iv) the epidermis of eight cases showed scattered staining with anti-pSTAT1 antibody, and (v) six cases were positive for HLA-DR membrane expression.<\/jats:p>\n                  <jats:p>Conclusions These data indicated that Th2 cytokines related to STAT6 activation together with some unknown stimuli that activate STAT3 play a principal role in the pathogenesis of PN.<\/jats:p>","DOI":"10.1111\/j.1365-2133.2011.10498.x","type":"journal-article","created":{"date-parts":[[2011,6,30]],"date-time":"2011-06-30T09:46:46Z","timestamp":1309427206000},"page":"990-996","source":"Crossref","is-referenced-by-count":105,"title":["Nuclear localization of activated STAT6 and STAT3 in epidermis of prurigo nodularis"],"prefix":"10.1093","volume":"165","author":[{"given":"S.","family":"Fukushi","sequence":"first","affiliation":[{"name":"Department of Dermatology, Graduate School of Medicine, Tohoku University, 1-1 Seiryo-cho, Aoba-ku, Sendai 980-8574, Miyagi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Yamasaki","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Graduate School of Medicine, Tohoku University, 1-1 Seiryo-cho, Aoba-ku, Sendai 980-8574, Miyagi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Aiba","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Graduate School of Medicine, Tohoku University, 1-1 Seiryo-cho, Aoba-ku, Sendai 980-8574, Miyagi, 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