Reference - Detail
RRC ID | 68722 |
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Author | Fukuda K, Ishida W, Tanaka H, Harada Y, Matsuda A, Ebihara N, Fukushima A. |
Title | Alarmins from corneal epithelial cells upregulate CCL11 and VCAM-1 in corneal fibroblasts. |
Journal | Invest Ophthalmol Vis Sci |
Abstract |
PURPOSE:Severe ocular allergic diseases are characterized by pronounced conjunctival inflammation triggered by T helper 2 (Th2) cells and corneal epithelial damage induced by eosinophils. To examine the role of alarmins released by damaged corneal epithelial cells in tissue eosinophilia, we investigated the effects of a supernatant derived from necrotic human corneal epithelial (HCE) cells on expression of the chemokine CCL11 (eotaxin) and the adhesion molecule VCAM-1 in human corneal fibroblasts. METHODS:An alarmin preparation was obtained as the material released from HCE cells after three cycles of freezing and thawing. CCL11 released into culture medium and cell surface expression of VCAM-1 were measured with enzyme-linked immunosorbent assays, and the amounts of CCL11 and VCAM-1 mRNAs were quantitated by reverse transcription and real-time polymerase chain reaction analysis. Signaling by the transcription factor NF-κB was evaluated by immunoblot and immunofluorescence analyses. RESULTS:The combination of the necrotic HCE cell supernatant and either interleukin (IL)-4 or IL-13 induced synergistic increases in CCL11 release, VCAM-1 expression, and the abundance of CCL11 and VCAM-1 mRNAs in corneal fibroblasts. The necrotic HCE cell supernatant also induced NF-κB activation in corneal fibroblasts, whereas an inhibitor of NF-κB and IL-1 receptor antagonist each attenuated CCL11 release induced by the alarmin preparation and either IL-4 or IL-13. CONCLUSIONS:Alarmins including IL-1 released from necrotic corneal epithelial cells cooperate with Th2 cytokines to induce CCL11 production and VCAM-1 expression in corneal fibroblasts, and may thereby play an important role in tissue eosinophilia associated with ocular allergic diseases. |
Volume | 54(8) |
Pages | 5817-23 |
Published | 2013-8-27 |
DOI | 10.1167/iovs.13-11969 |
PII | iovs.13-11969 |
PMID | 23920370 |
MeSH | Chemokine CCL11 / metabolism* Cytokines / physiology* Enzyme-Linked Immunosorbent Assay Epithelium, Corneal / metabolism* Fibroblasts / metabolism* Humans Interleukin-13 / physiology Interleukin-4 / physiology Keratoconjunctivitis / metabolism* NF-kappa B / metabolism Necrosis / metabolism RNA, Messenger / metabolism Real-Time Polymerase Chain Reaction Signal Transduction / physiology Vascular Cell Adhesion Molecule-1 / metabolism* |
IF | 3.47 |
Resource | |
Human and Animal Cells | HCE-T(RCB2280) |