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Activation of the epidermal growth factor receptor in optic nerve astrocytes leads to early and transient induction of cyclooxygenase-2.

Abstract：

PURPOSE:The epidermal growth factor receptor (EGFR) appears in astrocytes after neural injury. The authors' laboratory has reported the presence of EGFR in glaucomatous optic nerves. The activation of EGFR is often associated with induction of cyclooxygenase (COX)-2. In this study, the induction of COX-2 pathway in rat optic nerve astrocytes was investigated. METHODS:Induction of COX-2 was determined by immunoblot and immunocytochemistry in optic nerve astrocytes stimulated with EGF. EGF-induced prostaglandin (PG)E(2) release into the culture medium was assayed by ELISA. The effects of the EGFR tyrosine kinase inhibitor, AG1478, were studied on COX-2 expression and PGE(2) synthesis. In rat optic nerve transection and a rat optic nerve explant culture model, the relationship between the expression of COX-2 and activation of EGFR was examined. RESULTS:Activation of EGFR caused the rapid and transient induction of COX-2 in optic nerve astrocytes. The level of COX-2 was rapidly upregulated in optic nerves after axotomy and in an optic nerve explant culture model. When induced, COX-2 localized to the nuclear membrane of the astrocytes. When COX-2 was induced in response to activation of EGFR, the activated astrocytes produced and released the proinflammatory mediator, PGE(2), in a time-dependent manner. EGF-stimulated induction of COX-2 protein and synthesis of PGE(2) were abolished by the EGFR tyrosine kinase inhibitor AG1478. The stimulatory action of EGF on release of PGE(2) was inhibited by the COX-2-selective inhibitor NS398. CONCLUSIONS:The data demonstrate that the activation of EGFR in optic nerve astrocytes leads to the induction of the immediate early gene COX-2 and subsequent signaling through the synthesis of PGE(2). This early signal of neural tissue damage may be important in setting up secondary events in the damaged tissue.

journal_name

Invest Ophthalmol Vis Sci

journal_title

Investigative ophthalmology & visual science

authors

Zhang X,Neufeld AH

doi

10.1167/iovs.04-1473

keywords:

subject

Has Abstract

pub_date

2005-06-01 00:00:00

pages

2035-41

issue

eissn

0146-0404

issn

1552-5783

pii

46/6/2035

journal_volume

pub_type

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Activation of the epidermal growth factor receptor in optic nerve astrocytes leads to early and transient induction of cyclooxygenase-2.