title: Specific substance of Maruyama (SSM) suppresses immune responses in atopic dermatitis-like skin lesions in DS-Nh mice by modulating dendritic cell functions.
abstract: BACKGROUND
  Specific substance of Maruyama (SSM) is a carcinostatic immunotherapeutic agent extracted from Mycobacterium tuberculosis. The efficacy of SSM induced interleukin(IL)-12 and IFN-γ production, and inhibition of IL-4, resulting in a shift from Th2 to Th1 in vivo.
  
  
  OBJECTIVE
  The DS-Nh mice are a model of human atopic dermatitis (AD), which spontaneously develop dermatitis under conventional conditions. In this study, to determine whether SSM can prevent the development of skin lesions in a murine model of AD.
  
  
  METHODS
  DS-Nh mice were injected with SSM 5 days per week for 11 weeks. Pharmacological, histological and serological studies were performed to investigate the therapeutic effect of SSM for DS-Nh mice. Analysis of cytokines responses to SSM using quantitative RT-PCR and flow cytometry were also performed to evaluate their therapeutic mechanisms in these AD model mice.
  
  
  RESULTS
  Clinically, erythema, erosions, excoriation, and edema were observed in DS-Nh mice at 16 weeks of age, which advanced with age. Histologically, the relative number of mast cells increased in DS-Nh mice. SSM treatment alleviated the clinical and histological findings in accord with reduced serum IgE level, and increased IgG2a level. TSLP expression was not induced, but IL-1β, IL-12, IL-17A, and IFN-γ were induced in SSM-treated DS-Nh mice. Overall, SSM treatments increased the number of activated DCs in lesions. SSM induced CD80, CD86, and MHC class II expression on bone marrow-derived DCs.
  
  
  CONCLUSIONS
  SSM enhanced IL-12 production, but suppressed TSLP expression, resulting in a shift from Th2 to Th1 responses. This shift suppressed AD-like skin lesions in a similar fashion as the BCG vaccine. Therefore, SSM may be a useful adjuvant for suppressing skin lesions in AD models.
authors.affiliation: Department of Dermatology, Nippon Medical School, 1-1-5 Sendagi, Bunkyou-ku, Tokyo 113-8603, Japan. tmitsu@tymc.twmu.ac.jp
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Mitsuishi
authors.forename: Kenji
authors.initials: K
authors.lastname: Kabashima
authors.forename: Hideaki
authors.initials: H
authors.lastname: Tanizaki
authors.forename: Ikuroh
authors.initials: I
authors.lastname: Ohsawa
authors.forename: Fumino
authors.initials: F
authors.lastname: Oda
authors.forename: Yuko
authors.initials: Y
authors.lastname: Yamada
authors.forename: Yilinuer
authors.initials: Y
authors.lastname: Halifu
authors.forename: Seiji
authors.initials: S
authors.lastname: Kawana
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Kato
authors.forename: Kazumi
authors.initials: K
authors.lastname: Iida
mesh_terms: D000818:Animals; D001483:Base Sequence; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology* / Q000473:pathology; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007155:Immunologic Factors / Q000627:therapeutic use*; D008055:Lipids / Q000627:therapeutic use*; D008297:Male; D008351:Mannans / Q000627:therapeutic use*; D051379:Mice; D008812:Mice, Hairless; D008817:Mice, Mutant Strains; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016207:Cytokines; D007074:Immunoglobulin G; D007155:Immunologic Factors; D008055:Lipids; D008351:Mannans; D012333:RNA, Messenger; C031208:specific substance maruyama; D007073:Immunoglobulin E