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Published online before print January 24, 2008
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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.1107783

Received for publication November 20, 2007.
Revised December 21, 2007.
Accepted for publication December 23, 2007.

Article

C-Jun NH2 terminal kinase (JNK) is an essential mediator of Toll-like receptor 2-induced corneal inflammation

Gautam Adhikary , Yan Sun , and Eric Pearlman @

Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, Ohio, USA

@ To whom correspondence should be addressed. E-mail: Eric.Pearlman{at}case.edu.


  Abstract

TLRs play an important role in the host inflammatory response to bacteria and bacterial products by activating a cascade of intracellular events leading to production of proinflammatory and chemotactic cytokines. To determine the role of MAPKs in TLR- induced corneal inflammation, we stimulated human corneal epithelial (HCE) cells with TLR2 ligands, tripalmitoyl-S-glycero-Cys-(Lys)4 (Pam3Cys) or inactivated Staphylococcus aureus, and examined the time course of expression of MAPKs and the effect of MAPK inhibition on IkB{alpha} degradation and CXC chemokine production. We found that S. aureus and Pam3Cys stimulate phosphorylation of JNK, p38 MAPK, and ERK within 4 h and that blockade of JNK, but not p38 or ERK phosphorylation, had an inhibitory effect on IkB{alpha} degradation and CXC chemokine production. To determine if JNK is also important in TLR2-induced corneal inflammation in vivo, we examined JNK1-/- mice and pharmacological inhibitors in a murine model of inflammation induced by TLR activation of the corneal epithelium. The inflammatory response is characterized by neutrophil recruitment to the corneal stroma and development of corneal haze. We found that TLR-2-induced corneal inflammation was significantly impaired in JNK1-/- mice compared with control mice and in mice treated with the JNK inhibitor. Taken together with results from HCE cells, these findings demonstrate that JNK has an essential role in TLR2-induced corneal inflammation.

Key Words: TLR2 • S. aureus • corneal epithelial cells • inflammation • MAP kinase • neutrophil • chemokines • innate immunity




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J. Leukoc. Biol., June 1, 2008; 83(6): 1512 - 1521.
[Abstract] [Full Text] [PDF]


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