title: Augmentation of monocyte interleukin-8 production by psoralen/UVA-treated CD4+ T cells.
abstract: Treatment of cells with psoralen and ultraviolet A light (UVA) modulates their cytokine production. As extracorporeal photochemotherapy has been reported to induce cytokine production by monocytes, we quantified interleukin-8 (IL-8), a representative chemokine produced by monocytes, in culture supernatants from human peripheral blood mononuclear cells (PBMC) treated with 8-methoxypsoralen (8-MOP) and UVA. Lipopolysaccharide stimulated IL-8 production in 8-MOP-phototreated PBMC more efficiently than those untreated or treated with 8-MOP or UVA. More interestingly, when cultured with T-cell-stimulating anti-CD3 and anti-CD28 antibodies, 8-MOP/UVA-treated PBMC produced enhanced amounts of IL-8 with an increased level of IL-8 mRNA expression. Depletion of CD4 but not CD8 T cells from PBMC abrogated this augmented IL-8 elaboration, and CD4 T cells per se secreted no substantial amount of IL-8 even upon CD3/CD28 stimulation. Thus, 8-MOP/UVA-treated CD4 T cells stimulated monocytes to secrete IL-8. The IL-8 overproduction was induced by direct contact of monocytes with 8-MOP/UVA-treated CD4 T cells but not by cytokines from the treated CD4 T cells. These findings imply that in extracorporeal photochemotherapy, monocytes effectively produce IL-8 by cell-to-cell contact with 8-MOP/UVA-treated malignant CD4 T cells. The augmentation of monocyte cytokine/chemokine production by 8-MOP/UVA may be one of the mechanisms underlying the therapeutic efficacy of extracorporeal photochemotherapy.
authors.affiliation: Department of Dermatology, Photon Medical Research Center, Hamamatsu University School of Medicine, Hamamatsu, Japan. tokuray@hama-med.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Tokura
authors.forename: N
authors.initials: N
authors.lastname: Seo
authors.forename: M
authors.initials: M
authors.lastname: Tomida
authors.forename: M
authors.initials: M
authors.lastname: Sarukawa
authors.forename: H
authors.initials: H
authors.lastname: Hashizume
authors.forename: M
authors.initials: M
authors.lastname: Takigawa
authors.forename: S
authors.initials: S
authors.lastname: Moriwaki
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000502:physiology* / Q000528:radiation effects; D023201:CD40 Ligand / Q000378:metabolism; D002450:Cell Communication / Q000502:physiology; D002478:Cells, Cultured; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008730:Methoxsalen / Q000494:pharmacology*; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D014466:Ultraviolet Rays
chemical_list: D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D017252:CD3 Complex; D016209:Interleukin-8; D008070:Lipopolysaccharides; D023201:CD40 Ligand; D008730:Methoxsalen