title: Cyclosporin increases granulocyte/macrophage colony-stimulating factor (GM-CSF) activity and gene expression in murine keratinocytes.
abstract: Keratinocytes produce multiple cytokines in response to a variety of stimuli. The release of interleukin 1 (IL-1) from keratinocytes may be significant in initiation of cutaneous inflammation, and the presence of granulocyte/macrophage colony-stimulating factor (GM-CSF) is thought to be important in the regulation of antigen-presenting function by epidermal Langerhans cells. Because cyclosporin inhibits interleukin 2 release from T cells, it has been suggested that cyclosporin may function as an anti-inflammatory agent within the epidermis through inhibition of keratinocyte cytokine release. This investigation examined the direct effect of cyclosporin on the production of GM-CSF by murine keratinocytes and the keratinocyte cell line PAM 212. GM-CSF bioactivity increased in cell supernatants from keratinocytes exposed in vitro to 1 microgram/ml cyclosporin for up to 24 h. GM-CSF and IL-1 mRNA levels in keratinocytes cultured under similar conditions or in the presence of lipopolysaccharide also increased. The lack of inhibition of GM-CSF expression following cyclosporin treatment is consistent with recent observations in T cells and is opposite to the effect of cyclosporin on interleukin 2.
authors.affiliation: Department of Dermatology, Massachusetts General Hospital East, Charlestown 02129.
authors.forename: R L
authors.initials: RL
authors.lastname: Gallo
authors.forename: S
authors.initials: S
authors.lastname: Grabbe
authors.forename: S S
authors.initials: SS
authors.lastname: Choi
authors.forename: P
authors.initials: P
authors.lastname: Bleicher
authors.forename: R D
authors.initials: RD
authors.lastname: Granstein
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003524:Cyclosporins / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics; D007375:Interleukin-1 / Q000235:genetics; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D003524:Cyclosporins; D007375:Interleukin-1; D012333:RNA, Messenger; D016178:Granulocyte-Macrophage Colony-Stimulating Factor