Staphylococcus aureus protein A induced inflammatory response in human corneal epithelial cells.
In the present study, we examined the role of Staphylococcus aureus protein A (SpA) in inducing inflammatory response in human corneal epithelial cells (HCECs). Exposure of HCECs to SpA induces rapid NF-kappaB activation and secretion of proinflammatory cytokine/chemokines (TNF-alpha and IL-8) in both concentration and time-dependent manner. Challenge of HCECs with live SpA(-/-) mutant S. aureus strains resulted in significantly reduced production of the cytokines when compared to the wild-type S. aureus strain. SpA also elicited the activation of MAP Kinases P38, ERK, but not JNK, in HCECs. SpA-induced production of proinflammatory cytokine were completely blocked by the NF-kappaB and p38 inhibitors and partially inhibited by the Jnk inhibitor. Pretreatment with anti-TLR2 neutralizing antibody had no effect on SpA-induced inflammatory response in HCECs, suggesting that this response is independent of TLR2 signaling. Moreover, unlike TLR2 ligands, SpA failed to induce the expression of antimicrobial peptides (hBD2 and LL-37) in HCECs. These studies indicate that SpA is a S. aureus virulence factor that stimulates HCEC inflammatory response through a pathway distinct from TLR2 in HCECs.
Kumar
Ashok
A
The Kresge Eye Institute, Department of Ophthalmology, Wayne State University School of Medicine, Detroit, MI 48201, USA. akuma@med.wayne.edu
Tassopoulos
Alexander Mark
AM
Li
Qiong
Q
Yu
Fu-Shin X
FS
D004789:Enzyme Activation; D019573:Epithelium, Corneal / Q000187:drug effects*; D016209:Interleukin-8 / Q000378:metabolism; D007634:Keratitis / Q000139:chemically induced*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D013205:Staphylococcal Protein A / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000235:genetics; D051195:Toll-Like Receptor 2 / Q000187:drug effects / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016209:Interleukin-8; D016328:NF-kappa B; D013205:Staphylococcal Protein A; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; D020928:Mitogen-Activated Protein Kinases