| TRPV1 activation is required for hypertonicity-stimulated inflammatory cytokine release in human corneal epithelial cells. | |
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MedLine Citation:
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PMID: 20739465 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: To determine whether hypertonic stress promotes increases in inflammatory cytokine release through transient receptor potential vanilloid channel type 1 (TRPV1) signaling pathway activation in human corneal epithelial cells (HCECs). METHODS: Hyperosmotic medium was prepared by supplementing isotonic Ringers solution with sucrose. Ca2+ signaling was measured in fura2-AM-loaded HCECs using a single-cell fluorescence imaging system. Western blot analysis evaluated the phosphorylation status of EGFR, ERK, p38 MAPK, and nuclear factor (NF)-κB. ELISA assessed the effect of TRPV1 activation on the release of IL-6 and IL-8. RESULTS: A 450 mOsm hypertonic stress elicited 2-fold Ca2+ transients that were suppressed by the TRPV1-selective antagonists capsazepine and JYL 1421. Such transients were enhanced by PGE2. Hypertonicity-induced EGF receptor (EGFR) transactivation was suppressed by preincubating HCECs with capsazepine, matrix metalloproteinase 1 (MMP1) inhibitor TIMP-1, broad-spectrum MMP inhibitor GM 6001, heparin-bound (HB)-EGF inhibitor CRM 197, or EGFR inhibitor AG 1478. ERK and p38 MAPK and NF-κB activation after EGFR transactivation occurred in tonicity and in a time-dependent manner. Hypertonicity-induced increases in IL-6 and IL-8 releases were suppressed by exposure to capsazepine, AG 1478, ERK inhibitor PD 98059, p38 inhibitor SB 203580, or NF-κB inhibitor PDTC. CONCLUSIONS: Hypertonic stress-elicited TRPV1 channel stimulation mediates increases in a proinflammatory cytokine IL-6 and a chemoattractant IL-8 by eliciting EGFR transactivation, MAPK, and NF-κB activation. Selective drug modulation of either TRPV1 activity or its signaling mediators may yield a novel approach to suppressing inflammatory responses occurring in dry eye syndrome. |
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Authors:
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Zan Pan; Zheng Wang; Hua Yang; Fan Zhang; Peter S Reinach |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2011-01-21 |
Journal Detail:
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Title: Investigative ophthalmology & visual science Volume: 52 ISSN: 1552-5783 ISO Abbreviation: Invest. Ophthalmol. Vis. Sci. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-01-24 Completed Date: 2011-02-25 Revised Date: 2011-08-01 |
Medline Journal Info:
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Nlm Unique ID: 7703701 Medline TA: Invest Ophthalmol Vis Sci Country: United States |
Other Details:
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Languages: eng Pagination: 485-93 Citation Subset: IM |
Affiliation:
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Department of Biological Sciences, College of Optometry, State University of New York, New York, New York 10065, USA. zap2001@med.cornell.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Blotting, Western Calcium / metabolism Capsaicin / analogs & derivatives, pharmacology Cells, Cultured Enzyme Inhibitors / pharmacology Enzyme-Linked Immunosorbent Assay Epithelium, Corneal / drug effects*, metabolism Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors, metabolism Fura-2 / analogs & derivatives Humans Hypertonic Solutions / pharmacology* Interleukin-6 / metabolism* Interleukin-8 / metabolism* Microscopy, Fluorescence NF-kappa B / antagonists & inhibitors, metabolism Phosphorylation Receptor, Epidermal Growth Factor / metabolism Signal Transduction Stress, Physiological Sulfonamides / pharmacology TRPV Cation Channels / antagonists & inhibitors, metabolism* Thiourea / analogs & derivatives, pharmacology Time Factors p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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EY04795/EY/NEI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 0/Hypertonic Solutions; 0/Interleukin-6; 0/Interleukin-8; 0/JYL 1421; 0/NF-kappa B; 0/Sulfonamides; 0/TRPV Cation Channels; 0/TRPV1 protein, human; 0/capsazepine; 105344-37-4/fura-2-am; 404-86-4/Capsaicin; 62-56-6/Thiourea; 7440-70-2/Calcium; 96314-98-6/Fura-2; EC 2.7.10.1/EGFR protein, human; EC 2.7.10.1/Receptor, Epidermal Growth Factor; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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