title: Lipoteichoic acid-related molecule derived from the streptococcal preparation, OK-432, which suppresses atopic dermatitis-like lesions in NC/Nga mice.
abstract: Bacterial stimulation may serve to control atopic disorders such as atopic dermatitis (AD) through inducement of Th1 cell-mediated immune response. The lipoteichoic acid (LTA)-related molecule (okLTA) from streptococcal preparation, OK-432, has been shown to be a potent Th1 inducer through the action of IL-12. Examination was made of the therapeutic effects of this okLTA injected intra- and/or subcutaneously into AD-like lesions in NC/Nga mice, particularly in the vicinity of the suppressor of cytokine signaling (SOCS) regulatory pathways. Using immunohistochemical staining with IL-4/IL-12p40 and phosphorylated STAT6/p-STAT4 and RT-PCR for IL-4/IL-12p40, STAT6/STAT4 and mRNA expression and in situ hybridization of SOCS3 and 5, evaluation was made of the immunoregulatory effects of this okLTA in the treatment of spontaneous AD-like lesions in NC/Nga mice. Following the injection of okLTA, remarkable improvement in the lesions of NC/Nga mice was noted. In okLTA-treated skin, IL-12p40/p-STAT4 positive cellular infiltration was extensive while IL-4/p-STAT6 positive cell infiltration was seen to diminish considerably, compared to untreated NC mice. SOCS3 in situ expression in okLTA-treated mice was noted to be significantly less compared to untreated NC mice, in which the expression was prominent. SOCS5 in situ expression was rather, though not significantly, strong in okLTA-treated mice. okLTA treatment is clearly shown to induce Th1 cellular response and down-regulate immune response in the Th2 pathway through SOCS3 reduction in AD-like lesions of NC/Nga mice. The present results demonstrate that bacterial wall components such as okLTA should serve as an effective new therapeutic approach for treating AD.
authors.affiliation: Department of Dermatology, Nagasaki University Graduate School of Medicine, 1-7-1 Sakamoto, 852-8501 Nagasaki, Japan, ngu-yashoriu@r7.dion.ne.jp
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Horiuchi
authors.forename: Sangjae
authors.initials: S
authors.lastname: Bae
authors.forename: Ichiro
authors.initials: I
authors.lastname: Katayama
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Oshikawa
authors.forename: Masato
authors.initials: M
authors.lastname: Okamoto
authors.forename: Mitsunobu
authors.initials: M
authors.lastname: Sato
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008070:Lipopolysaccharides / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D009000:Monocytes / Q000378:metabolism; D010844:Picibanil / Q000737:chemistry / Q000494:pharmacology*; D050800:STAT6 Transcription Factor / Q000187:drug effects*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000187:drug effects; D013682:Teichoic Acids / Q000737:chemistry / Q000494:pharmacology*; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D050800:STAT6 Transcription Factor; C491411:Socs3 protein, mouse; C485811:Socs5 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D013682:Teichoic Acids; D010844:Picibanil; C009900:lipoteichoic acid