title: Constitutive secretion of chemokines by cultured human trabecular meshwork cells.
abstract: Trabecular meshwork endothelial (TME) cells secrete a number of factors, such as enzymes and cytokines, which modulate the functions of the cells and the extracellular matrix of the conventional aqueous outflow pathway. TME cells usually secrete these factors in response to stimuli such as mechanical stretching, laser irradiation and pro-inflammatory cytokines. Here, we report that cultured human TME cells isolated from two non-glaucomatous individuals secrete significant quantities of the chemotactic cytokines IL8, CXCL6 and MCP1 in the absence of any stimulation. The secretion of these chemokines was augmented by treatment with the pro-inflammatory cytokines TNFalpha and IL1beta. By way of comparison, there was little or very low production of the three chemokines by human non-pigmented ciliary epithelial cells in the absence of stimulation. Our findings provide support to our recent observations that monocytes, presumably under the influence of chemotactic signals, circulate through the trabecular meshwork in the normal state and also that cytokines regulate the permeability of Schlemm's canal endothelial cells. In addition, the fact that normal TME cells constitutively secrete chemotactic cytokines strengthens the notion that cytokines play a key role in the homeostasis of the outflow of the aqueous humor and, possibly, in the pathogenesis of glaucoma.
authors.affiliation: Department of Ophthalmology, University of California, San Francisco, 10 Koret Way, San Francisco, CA 94143-0730, USA.
authors.forename: Amde Selassie
authors.initials: AS
authors.lastname: Shifera
authors.forename: Sheetal
authors.initials: S
authors.lastname: Trivedi
authors.forename: Phuonglan
authors.initials: P
authors.lastname: Chau
authors.forename: Lucia H
authors.initials: LH
authors.lastname: Bonnemaison
authors.forename: Rumiko
authors.initials: R
authors.lastname: Iguchi
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Alvarado
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism*; D054427:Chemokine CXCL6 / Q000378:metabolism*; D002924:Ciliary Body / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D016209:Interleukin-8 / Q000378:metabolism*; D014129:Trabecular Meshwork / Q000187:drug effects / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: C111835:CCL2 protein, human; C515503:CXCL6 protein, human; C508606:CXCL8 protein, human; D018932:Chemokine CCL2; D054427:Chemokine CXCL6; D053583:Interleukin-1beta; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha