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Human Cathelicidin (LL-37), a Multifunctional Peptide, is Expressed by Ocular Surface Epithelia and has Potent Antibacterial and Antiviral Activity Export

Current Eye Research, Vol. 30, No. 5. (2005), pp. 385-394.

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adenovirus cathelicidin herpes_simplex_virus hsv innate_immunity ll-37 virus

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<i>Purpose</i>: This study determined whether LL-37 (cathelicidin) is expressed by conjunctival and corneal epithelia as part of ocular host defense. The antimicrobial activity of LL-37 was also assessed <i>in vitro</i> against <i>Pseudomonas aeruginosa</i> (PA), <i>Staphylococcus aureus</i> (SA), <i>Staphylococcus epidermidis</i> (SE), herpes simplex virus type 1 (HSV-1), and adenovirus (Ad). <i>Methods</i>: Expression of LL-37/hCAP 18 mRNA and LL-37 protein was determined by reverse transcriptionpolymerase chain reaction (RT-PCR) and immunoblotting, respectively, in scraped human corneal epithelium and primary cultured human corneal and conjunctival epithelial cells. The EC<sub>50</sub> values for three strains of PA and one each of SA and SE were determined for LL-37. LL-37 antiviral inhibition of HSV-1 and adenovirus was assessed by direct inactivation assays. Toxicity of LL-37 to A549 cells was evaluated by a MTT assay. <i>Results</i>: LL-37/hCAP18 mRNA and LL-37 peptide were expressed by human corneal and conjunctival epithelial cells. Antibacterial activity for LL-37 was demonstrated (EC<sub>50</sub> values for the three PA strains were 2.8 ± 1.3, 1.9 ± 0.3, and 3.6 ± 2.1; for SA: 1.6 ± 1.5; for SE: 1.3 ± 1.9 &b.mu; g/ml). LL-37 produced a significant reduction (p < 0.001 ANOVA) in HSV-1 and Ad19 viral titers with distinctly different time-kill curves (p < 0.001). LL-37 (up to 111 &b.mu; M) produced no toxicity in A549 cells. <i>Conclusions</i>: Corneal and conjunctival epithelia express LL-37 as part of mucosal innate immunity to protect against bacterial and viral ocular infections.


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