title: Interleukin-7 (IL-7) induces retinal pigment epithelial cell MCP-1 and IL-8.
abstract: The neuroectodermally-derived retinal pigment epithelium (RPE) forms part of the blood-retina barrier where it is strategically-positioned to regulate leukocyte infiltration in retinal diseases. Activated human RPE cells possess several functions enabling them to perform this role including expression of HLA-DR antigens, production of intercellular adhesion molecule-1, and secretion of monocyte chemotactic protein-1 and interleukin-8. In this study, we examined the ability of interleukin-7 to induce RPE-derived monocyte chemotactic protein-1 and interleukin-8 and assessed the potentiating effects of interleukin-7 on interleukin-1 beta- and tumor necrosis factor-alpha-induced RPE monocyte chemotactic protein-1 and interleukin-8 production. Human RPE cells incubated with interleukin-7 (1-100 ng ml-1) for 24 hr secreted significant levels of antigenic RPE monocyte chemotactic protein-1 and interleukin-8 in a dose-dependent fashion interleukin-7 (P < 0.05). RPE costimulation with interleukin-7 and interleukin-1 beta (2 ng ml-1) or tumor necrosis factor-alpha (2 ng ml-1) resulted in additive increases (P < 0.05) in secreted monocyte chemotactic protein-1 and interleukin-8. Steady-state RPE monocyte chemotactic protein-1 mRNA was substantially increased by interleukin-7 (1-100 ng ml-1), while RPE interleukin-8 mRNA was mildly elevated by higher doses of interleukin-7 (10-100 ng ml-1). Time-dependent increases in RPE monocyte chemotactic protein-1 and interleukin-8 mRNA were noted. RPE monocyte chemotactic protein-1 mRNA peaked at 2 hr and decreased over 8 hr and 24 hr. Whereas, RPE interleukin-8 mRNA was perceptible at 2 hr, maximal at 8 hr, and reduced by 24 hr. Interleukin-7 potentiated interleukin-1 beta-induced monocyte chemotactic protein-1 and interleukin-8 steady-state mRNA expression at all interleukin-7 concentrations. Interleukin-7 potentiated tumor necrosis factor-alpha-induced RPE monocyte chemotactic protein-1 steady-state mRNA expression at all doses of interleukin-7 while only high dose interleukin-7 (100 ng ml-1) enhanced tumor necrosis factor-alpha-induced RPE interleukin-8 steady-state gene expression. Our data show that interleukin-7 is a primary stimulus of RPE monocyte chemotactic protein-1 and interleukin-8. This is one of the first reports demonstrating: (1) interleukin-7 induction of monocyte chemotactic protein-1 in any cell type, and (2) interleukin-7 induction of interleukin-8 in resident, tissue-based cells. These studies suggest that interleukin-7 potentiation of interleukin-1 beta and tumor necrosis factor-alpha-induced RPE monocyte chemotactic protein-1 and IL-8 may be important for the elicitation of leukocyte chemotaxins in diseased retinal tissue when only low ambient levels of individual pro-inflammatory cytokines are present.
authors.affiliation: Department of Ophthalmology, University of Michigan, Ann Arbor 48105, USA.
authors.forename: V M
authors.initials: VM
authors.lastname: Elner
authors.forename: S G
authors.initials: SG
authors.lastname: Elner
authors.forename: T J
authors.initials: TJ
authors.lastname: Standiford
authors.forename: N W
authors.initials: NW
authors.lastname: Lukacs
authors.forename: R M
authors.initials: RM
authors.lastname: Strieter
authors.forename: S L
authors.initials: SL
authors.lastname: Kunkel
mesh_terms: D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology; D015851:Interleukin-7 / Q000494:pharmacology / Q000502:physiology*; D016209:Interleukin-8 / Q000378:metabolism*; D010857:Pigment Epithelium of Eye / Q000276:immunology* / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D018932:Chemokine CCL2; D007375:Interleukin-1; D015851:Interleukin-7; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha