title: Inflammatory cytokines regulate secretion of VEGF and chemokines by human conjunctival fibroblasts: Role in dysfunctional tear syndrome.
abstract: Ocular surface inflammation is one of the primary mechanisms associated with dysfunctional tear syndrome (DTS), also known as dry eye disease. DTS, more prevalent in older populations, causes ocular discomfort and visual disturbance due to dryness on the surface layer in the eye. We used human conjunctival fibroblast cultures (HCJVF) to investigate the effects of inflammatory cytokines IFN-γ, TNF-α and IL-1β (ITI) on the secretions of VEGF and chemokines. Our results demonstrate the elevated secretion of angiogenic VEGF molecules by ITI without affecting anti-angiogenic molecules, PEDF, endostatin, thrombospondin and sVEGF-R1. The secretion of interferon-γ inducible chemokines, CXCL9, -10, -11 by HCJVF were significantly enhanced by ITI. Our in vitro study supports previously reported observations of elevated VEGF and chemokines in tear fluids of DTS patients, reiterating the role of inflammatory reactions in DTS.
authors.affiliation: Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, United States. Electronic address: naginenic@mail.nih.gov.
authors.forename: Chandrasekharam N
authors.initials: CN
authors.lastname: Nagineni
authors.affiliation: Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, United States.
authors.forename: Abitha
authors.initials: A
authors.lastname: William
authors.affiliation: Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892,United States.
authors.forename: Aswini
authors.initials: A
authors.lastname: Cherukuri
authors.affiliation: Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892,United States.
authors.forename: William
authors.initials: W
authors.lastname: Samuel
authors.affiliation: Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, United States.
authors.forename: John J
authors.initials: JJ
authors.lastname: Hooks
authors.affiliation: Department of Pathology, Johns Hopkins University, School of Medicine, Baltimore, MD 21287, United States.
authors.forename: Barbara
authors.initials: B
authors.lastname: Detrick
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D003228:Conjunctiva / Q000166:cytology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D015352:Dry Eye Syndromes / Q000276:immunology / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D007371:Interferon-gamma / Q000494:pharmacology; D053583:Interleukin-1beta / Q000494:pharmacology; D013666:Tears / Q000737:chemistry / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D018925:Chemokines; D016207:Cytokines; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D007371:Interferon-gamma
keywords: Chemokines; Conjunctival fibroblasts; Dysfunctional tear syndrome; Inflammation; VEGF