In addition to NF-κB activation, TLR ligands also induce the activation of other MAPKs, such as p38, JNK, and ERK and these signaling molecules are known to contribute towards inflammatory response in epithelial
Olaparib [17]. Our results that SpA induces the activation of p38 and ERK and inhibition of these two pathways completely blocked the SpA-induced cytokine secretion in HCECs suggesting that TLR ligands and SpA share some homology in terms of intracellular signaling pathway activation. TLR2 activation in HCECs not only induces the activation of NF-κB and the production of proinflammatory cytokines but also up-regulates the expression of several antimicrobial genes, such as hBD2, and LL-37. The expression of these antimicrobial molecules renders epithelial and infiltrated PMN the ability to kill invading bacteria. This enhanced innate defense is believed to play a role in limiting infection when host-pathogen interaction occurs. Interestingly, SpA, although is able to induce NF-κB activation and proinflammatory cytokine production, does not trigger the
expression of antimicrobial peptides in HCECs. Thus, targeting SpA triggered inflammatory response may have some advantage over TLR pathways as it may reduce inflammatory response without significantly affecting the innate defense mechanism in S. aureus-infected corneas. Thus, a better understanding of host-pathogen interaction in the cornea might provide molecular bases for the development of novel, specific therapies for prevention or treatment of infective keratitis.
