Bacterial keratitis is the serious corneal infection involving inflammation, but the proinflammatory effects of Gram-positive bacterial cell wall components on human corneal epithelial cells (HCECs) remain implicit. A20 serves as a crucial regulator in many systemic or topical inflammation. Herein, we firstly explore the effects on corneal epithelial inflammation and A20 expression of different cell wall components. Immortalized HCECs were treated with various concentrations of Staphylococcus aureus cell wall components (lipoteichoic acid [LTA], peptidoglycan, and staphylococcal protein A), with lipopolysaccharide (LPS) from Pseudomonas aeruginosa as a positive control. Only LTA and LPS significantly induced the phosphorylation of p65, p38, JNK, and ERK, along with increased IL-6, IL-8, and A20 expression. LTA (10 μg/mL) elicited the proinflammatory effect similar to LPS. Thus, we further investigated the role of A20 in the LTA-mediated inflammatory injury in HCECs. The A20 expression exhibited both time- and dose-dependent manner, and peaked at 4 h after LTA treatment. Reduced A20 expression exacerbated IL-6 and IL-8 levels induced by LTA, while increased A20 augmented their expression. Pretreatment with p65, p38, JNK, and ERK antagonists downregulated A20 expression, indicating NF-κB and MAPK pathways are required for A20 expression. A20 also suppressed NF-κB and MAPK pathways activation, confirmed by both A20-knockdown and A20-overexpressed HCECs following LTA induction. These findings suggest that LTA induces the A20 expression in HCECs due to its strong immunogenicity. A20 expression is pivotal in mitigating inflammatory response to Gram-positive bacterial infections through NF-κB and MAPK pathways, and reduced IL-6 and IL-8 levels.
Keywords: Corneal epithelial cells; Lipoteichoic acid; Mitogen-activated protein kinase (MAPK); Nuclear factor-κB (NF-κB); TNF-α-inducible protein 3 (TNFAIP3/A20).
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