title: Staphylococcal enterotoxin B upregulates expression of ICAM-1 molecules on IFN-gamma-treated keratinocytes and keratinocyte cell lines.
abstract: The effects of staphylococcal enterotoxin B (SEB), a Staphylococcus aureus-derived bacterial superantigen, on expression of intercellular adhesion molecule-1 (ICAM-1) were examined in cultured normal and transformed (DJM-1 cells) human keratinocytes by flow cytometry, confocal microscopy, digital image processing, and reverse transcriptase-polymerase chain reaction. SEB significantly upregulated ICAM-1 expression in the interferon-gamma (IFN-gamma)-pretreated, HLA-DR-positive normal keratinocytes and DJM-1 cells in a dose-dependent manner, but not in the untreated, HLA-DR-negative cells. Other toxins such as diphtheria and pertussis toxins did not have the effect. The distribution of SEB and HLA-DR molecules was identical on the IFN-gamma-treated, HLA-DR-positive DJM-1 cells by confocal microscopy. Digital image processing analysis demonstrated that SEB induced a transient increase of intracellular calcium concentration only in the IFN-gamma-treated DJM-1 cells. Pretreatment of the IFN-gamma-treated DJM-1 cells with anti-major histocompatibility complex class II monoclonal antibody completely blocked the effect of SEB. Furthermore, ICAM-1 mRNA was detected in the IFN-gamma-pretreated, SEB-exposed normal keratinocytes by reverse transcriptase-polymerase chain reaction. Our results demonstrate that SEB binds to keratinocytes, presumably via major histocompatibility complex class II molecules such as HLA-DR, triggers calcium mobilization, and induces the synthesis of ICAM-1 molecules. We speculate that, in various cutaneous disorders, SEB penetrates the epidermis and interacts with HLA-DR-positive keratinocytes to upregulate ICAM-1 expression, thus modulating the course of the inflammatory process.
authors.affiliation: Department of Dermatology, Hamamatsu University School of Medicine, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Wakita
authors.forename: Y
authors.initials: Y
authors.lastname: Tokura
authors.forename: F
authors.initials: F
authors.lastname: Furukawa
authors.forename: M
authors.initials: M
authors.lastname: Takigawa
mesh_terms: D000938:Antigen-Presenting Cells / Q000187:drug effects* / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004768:Enterotoxins / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007091:Image Processing, Computer-Assisted; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology*; D007424:Intracellular Fluid / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins; D012878:Skin Neoplasms / Q000473:pathology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D004768:Enterotoxins; D006684:HLA-DR Antigens; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1; C031818:enterotoxin B, staphylococcal; D007371:Interferon-gamma; D002118:Calcium