title: Modulation of T-lymphocyte proliferation by exogenous natural ceramides and sphingosylphosphorylcholine.
abstract: Sphingolipids such as ceramide and sphingosine are abundantly present in the stratum corneum of epidermis. In atopic stratum corneum, sphingosylphosphorylcholine (SPC) is present in association with a reduction in the amount of ceramides. We have previously shown that the cellular kinetics of T cells are affected by exogenous addition of sphingosine and synthetic ceramides, raising the possibility that sphingolipids diffusing from the stratum corneum modulate skin-infiltrating T cells. By using two natural ceramides and murine T cells, this study further clarified the conditions under which exogenous ceramides enhance the proliferation of T cells. KLH-specific T cell clones 28-4 and 24-2 proliferated in response to natural ceramides when cultured for 44-48 h in the presence of concanavalin A at 1 microg per ml. Elongation of culture periods adversely inhibited the T cell proliferation, suggesting the existence of an optimal exposure time. Augmentation of DNA synthesis by natural ceramides was more pronounced in tumor necrosis factor alpha (TNFalpha)-sensitive 28-4 cells than in less sensitive 24-2 cells, and TNFalpha-induced proliferation of 28-4 cells was suppressed by the concomitant addition of natural ceramides. Similar to ceramides, SPC augmented the proliferation of resting spleen cells. Our study suggests that ceramide modulation of T cell proliferation depends on the TNFalpha sensitivity and activation level of T cells and that SPC also has a mitogenic potential for T cells.
authors.affiliation: Department of Dermatology, Hamamatsu University School of Medicine, Japan. tokuray@hama-med.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Tokura
authors.forename: H
authors.initials: H
authors.lastname: Wakita
authors.forename: N
authors.initials: N
authors.lastname: Seo
authors.forename: F
authors.initials: F
authors.lastname: Furukawa
authors.forename: K
authors.initials: K
authors.lastname: Nishimura
authors.forename: M
authors.initials: M
authors.lastname: Takigawa
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002518:Ceramides / Q000494:pharmacology*; D003208:Concanavalin A / Q000494:pharmacology; D004261:DNA Replication / Q000187:drug effects; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D002518:Ceramides; D014409:Tumor Necrosis Factor-alpha; C005356:sphingosine phosphorylcholine; D010767:Phosphorylcholine; D003208:Concanavalin A; D013110:Sphingosine