title: Enhanced production of biologically active interleukin-1 alpha and interleukin-1 beta by psoriatic epidermal cells ex vivo: evidence of increased cytosolic interleukin-1 beta levels and facilitated interleukin-1 release.
abstract: The expression of interleukin (IL)-1 is altered in psoriatic lesions. However, little is known about the actual production of IL-1 alpha and IL-1 beta by psoriatic epidermal cells (EC). We monitored IL-1 in the extracellular, the membrane and the intracellular compartment of freshly isolated EC from untreated lesional psoriatic (PP) and normal healthy (NN) skin during non-stimulated short-term cultures, representing a psoriasis model ex vivo. Cytokines were measured using bioassays combined with neutralizing antibodies and enzyme-linked immunosorbent assay in parallel. PP EC released significantly increased amounts of biologically active IL-1 alpha and IL-1 beta in a ratio of 3:1, whereas NN EC only released IL-1 alpha. Also, the release of IL-6, but not of TNF-alpha, by PP EC was significantly increased. Membrane-associated IL-1 activity, analyzed using glutaraldehyde-fixed EC, was low and not unique to PP EC. The cytosol of PP EC contained significantly increased levels of immunoreactive IL-1 beta. Furthermore, PP EC displayed loss of membrane integrity, as determined by trypan blue exclusion and release of cytosolic lactate dehydrogenase. This facilitated release of intracellular IL-1. Depletion of CD45+ cells showed that intraepidermal leukocytes did not contribute to the production of IL-1. Our observations show that resident PP EC express enhanced IL-1 production ex vivo, which is due to an increased cytosolic IL-1 beta content and facilitated IL-1 release. This study provides the first evidence that PP EC can produce bioactive IL-1 beta.
authors.affiliation: Department of Immunology, Erasmus University Rotterdam, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Debets
authors.forename: J P
authors.initials: JP
authors.lastname: Hegmans
authors.forename: R J
authors.initials: RJ
authors.lastname: Troost
authors.forename: R
authors.initials: R
authors.lastname: Benner
authors.forename: E P
authors.initials: EP
authors.lastname: Prens
mesh_terms: D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000378:metabolism; D011565:Psoriasis / Q000378:metabolism*; D012867:Skin / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha