title: Decreased serum LL-37 and vitamin D3 levels in atopic dermatitis: relationship between IL-31 and oncostatin M.
abstract: BACKGROUND
  Skin lesions with atopic dermatitis (AD) are associated with dysregulated expression of LL-37 and enhanced expression of IL-22, thymic stromal lymphopoietin (TSLP), IL-25, IL-31, and oncostatin M. Vitamin D3 enhances LL-37 production in keratinocytes. This study aimed to examine the serum levels of LL-37 and vitamin D3 and their regulation of cytokine production in patients with AD.
  
  
  METHODS
  Serum levels of LL-37 and 25-hydroxyvitamin D3 were analyzed by ELISA. The effects of 1,25-dihydroxyvitamin D3 or LL-37 on cytokine production in T cells or keratinocytes were analyzed by ELISA and real-time PCR.
  
  
  RESULTS
  Serum levels of LL-37 and 25-hydroxyvitamin D3 were decreased in patients with AD compared to normal donors and were correlated in both groups. Serum levels of LL-37 correlated with those of oncostatin M and IL-31 in normal donors and patients with AD, while 25-hydroxyvitamin D3 levels did so only in normal donors. 1,25-dihydroxyvitamin D3 increased LL-37 production in human keratinocytes and neutrophils. 1,25-dihydroxyvitamin D3 and LL-37 enhanced the oncostatin M and IL-31 production in CD3/28-stimulated T cells, but did not alter IL-25 and TSLP production in TNF-α-stimulated keratinocytes. In CD3/28-stimulated T cells, 1,25-dihydroxyvitamin D3 reduced the IL-22 production, while LL-37 enhanced it. These effects of 1,25-dihydroxyvitamin D3 and LL-37 were suppressed by vitamin D receptor antagonist and pertussis toxin, respectively.
  
  
  CONCLUSIONS
  Systemic vitamin D3 levels are reduced in patients with AD, which may contribute to decreased systemic LL-37 levels. LL-37 may systemically potentiate the oncostatin M and IL-31 production in normal donors and patients with AD, while vitamin D3 may do so only in normal donors.
authors.affiliation: Department of Dermatology, School of Medicine, Teikyo University, Tokyo, Japan. nmk@med.teikyo-u.ac.jp
authors.forename: N
authors.initials: N
authors.lastname: Kanda
authors.forename: C S
authors.initials: CS
authors.lastname: Hau
authors.forename: Y
authors.initials: Y
authors.lastname: Tada
authors.forename: S
authors.initials: S
authors.lastname: Sato
authors.forename: S
authors.initials: S
authors.lastname: Watanabe
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000097:blood* / Q000276:immunology; D002478:Cells, Cultured; D002762:Cholecalciferol / Q000097:blood* / Q000276:immunology; D003876:Dermatitis, Atopic / Q000276:immunology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007378:Interleukins / Q000276:immunology / Q000378:metabolism*; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D053683:Oncostatin M / Q000276:immunology / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; C502187:IL31 protein, human; D007378:Interleukins; D053683:Oncostatin M; D002762:Cholecalciferol; D054804:Cathelicidins