title: Immunomodulatory effect of water soluble extract separated from mycelium of Phellinus linteus on experimental atopic dermatitis.
abstract: BACKGROUND
  Complementary and alternative medicine (CAM) is becoming a popular treatment for modulating diverse immune disorders. Phellinus linteus (P. linteus) as one of the CAMs has been used to modulate cancers, inflammation and allergic activities. However, little evidence has been shown about its underlying mechanism of action by which it exerts a beneficial role in dermatological disease in vivo. In this study, we examined the immunomodulatory effects of P. linteus on experimental atopic dermatitis (AD) and elucidated its action mechanism.
  
  
  METHODS
  The immunomodulatory effect of total extract of P. linteus on IgE production by human myeloma U266B1 cells was measured by ELISA. To further identify the effective components, P. linteus was fractionated into methanol soluble, water soluble and boiling water soluble extracts. Each extract was treated to U266B1 cells and primary B cells to compare their inhibitory effects on IgE secretion. To test the in vivo efficacy, experimental atopic dermatitis (AD) was established by alternative treatment of DNCB and house dust mite extract into BALB/c mice. Water soluble extract of P. linteus (WA) or ceramide as a positive control were topically applied to ears of atopic mouse every day for 2 weeks and progression of the disease was estimated by the following criteria: (a) ear thickness, clinical score, (b) serum total IgE, IgG and mite specific IgE level by ELSIA, (c) histological examination of ear tissue by H&E staining and (d) cytokine profile of total ear cells and CD4(+) T cells by real time PCR and ELSIA.
  
  
  RESULTS
  Treatment of total extracts of P. linteus to U266B1 inhibited IgE secretion. Among the diverse extracts of P. linteus, water soluble extract of P. linteus (WA) significantly reduced the IgE production in primary B cells and B cell line U266B1. Moreover, treatment of WA reduced AD symptoms such as ear swelling, erythema, and dryness and decreased recruitment of lymphocyte into the inflamed site. Interestingly WA treatment significantly reduced IgE level without affecting IgG levels and also down-regulated the levels of pathogenic cytokines (IL-4, IL-13, IL-12 and IFN-γ) and chemokines (CCL17 and CCL22) involved in AD development.
  
  
  CONCLUSIONS
  Our study indicates that protective effect of water soluble extract of P. linteus in atopic dermatitis is mediated by inhibiting IgE production and expression of AD associated pathogenic cytokines as well as chemokines, suggesting the beneficial effect of P. linteus to modulate allergic skin disease.
authors.affiliation: School of Life Sciences and Immune Synapse Research Center, Gwangju Institute of Science and Technology (GIST), 261 Cheomdan-gwagiro, Gwangju 500-712, Korea.
authors.forename: Ji Sun
authors.initials: JS
authors.lastname: Hwang
authors.forename: Ho-Keun
authors.initials: HK
authors.lastname: Kwon
authors.forename: Jung-Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: Jeonghae
authors.initials: J
authors.lastname: Rho
authors.forename: Sin-Hyeog
authors.initials: SH
authors.lastname: Im
mesh_terms: D000818:Animals; D001487:Basidiomycota / Q000737:chemistry* / Q000254:growth & development; D016207:Cytokines / Q000276:immunology; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000302:isolation & purification; D051379:Mice; D008807:Mice, Inbred BALB C; D025282:Mycelium / Q000737:chemistry / Q000187:drug effects; D000084682:Phellinus; D010936:Plant Extracts; D011134:Polysaccharides / Q000008:administration & dosage* / Q000302:isolation & purification
chemical_list: D016207:Cytokines; D007155:Immunologic Factors; C526145:Phellinus linteus extract; D010936:Plant Extracts; D011134:Polysaccharides; D007073:Immunoglobulin E