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(Investigative Ophthalmology and Visual Science. 2002;43:2272-2277.)
© 2002 by The Association for Research in Vision and Ophthalmology, Inc.

Lipoteichoic Acid Selectively Induces the ERK Signaling Pathway in the Cornea

Lingtao You1, Friedrich E. Kruse1, Susanne Bacher2 and M. Lienhard Schmitz3

1 From the Department of Ophthalmology, University of Heidelberg Medical School and 2 German Cancer Research Institute, Division of Immunochemistry (G0200), Heidelberg, Germany; and 3 University of Bern, Institute for Chemistry and Biochemistry, Bern, Switzerland.

PURPOSE. To identify signal transduction pathways and gene expression induced by the bacterial cell wall component lipoteichoic acid (LTA) in human corneal keratocytes.

METHODS. Human corneal keratocytes were cultured in the presence of 6.25 to 50 µg/ml LTA from Staphylococcus aureus. Induced DNA-binding of NF-{kappa}B was determined by electrophoretic mobility shift assays (EMSAs). Activation of MAP-kinase signaling pathways (p38, JNK-1/2, ERK-1/2, Elk 1, MEK-1/2, c-Raf) was evaluated by Western blotting using phospho-specific antibodies. To investigate the effect of LTA signaling on gene expression, keratocytes were transfected with a luciferase reporter gene under the control of serum response elements (SREs). LTA-induced gene expression was quantified using luciferase assays.

RESULTS. Exposure of various concentrations of LTA up to 24 hours did not lead to activation of NF-{kappa}B, whereas TNF-{alpha} potently induced this transcription factor. A systematic analysis of LTA-activated MAPK pathways revealed no significant effects on JNK and p38, but a dose- and time-dependent phosphorylation of members of the ERK pathway. Analysis of the ERK-activating signaling cascade showed LTA-induced phosphorylation of ERK-1, MEK1/2, and c-Raf. ERK activity resulted in an enhanced transcription of an SRE-controlled reporter gene.

CONCLUSIONS. LTA induces SRE-enhanced gene transcription in corneal keratocytes that is selectively mediated by the ERK pathway. Therefore, it seems possible that components of the bacterial cell wall such as LTA can alter the transcriptional program within the corneal stroma and thereby trigger an inflammatory response.




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A. Kumar, J. Zhang, and F.-S. X. Yu
Innate Immune Response of Corneal Epithelial Cells to Staphylococcus aureus Infection: Role of Peptidoglycan in Stimulating Proinflammatory Cytokine Secretion
Invest. Ophthalmol. Vis. Sci., October 1, 2004; 45(10): 3513 - 3522.
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Copyright © 2002 by the Association for Research in Vision and Ophthalmology