The Spectrum of Antimicrobial Peptide Expression at the Ocular Surface

McIntosh, Richard S.; Cade, Jennie E.; Al–Abed, M.; Shanmuganathan, Vijay; Gupta, Rajen K.; Bhan, A; Tighe, Patrick J.; Dua, Harminder S.

doi:10.1167/iovs.04-0607

Cited by 72 publications

(71 citation statements)

References 46 publications

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“…2,3,14,18,31-34,36,37 The current study reports for the first time that the epithelial cells of both the cornea and conjunctiva express this important effector of innate immunity. This discovery was initially reported in 2003 51 and has recently been confirmed in a report by Dua et al 52 Our discovery of LL-37 as a part of ocular mucosal defense complements previous studies that have demonstrated that α-defensins hBD-1, -2, and -3 are also secreted by conjunctival and corneal epithelium. 39-43,53 Taken together, these findings suggest that the ocular surface must be added to the growing list of mucosal surfaces throughout the body where multifunctional cationic peptides operate as part of innate immunity.…”

Section: Antiviral Activity Of Ll-37 and Scrambled Ll-37 Against Hsv-supporting

confidence: 83%

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

Gordon

Li-min

Romanowski

et al. 2005

Current Eye Research

226

190

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Purpose: 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 in vitro against Pseudomonas aeruginosa (PA), Staphylococcus aureus (SA), Staphylococcus epidermidis (SE), herpes simplex virus type 1 (HSV-1), and adenovirus (Ad). Methods: Expression of LL-37/hCAP 18 mRNA and LL-37 protein was determined by reverse transcription-polymerase chain reaction (RT-PCR) and immunoblotting, respectively, in scraped human corneal epithelium and primary cultured human corneal and conjunctival epithelial cells. The EC 50 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. Results: 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 50 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 μg/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 μM) produced no toxicity in A549 cells. Conclusions: 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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Section: Antiviral Activity Of Ll-37 and Scrambled Ll-37 Against Hsv-supporting

confidence: 83%

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

Gordon

Li-min

Romanowski

et al. 2005

Current Eye Research

226

190

View full text Add to dashboard Cite

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“…Expression of this defensin is also upregulated in the cornea in response to injury [106] and in the conjunctival epithelium of patients with dry eye [101,107] . Corneal and conjunctival epithelial cells also express hBD-3 [100,101,108] , but while some studies have indicated that expression of this defensin is inducible by TNF-␣ and interferon-␥ [42,43,109] , this was not observed in ocular surface epithelial cells [101] . Whilst McIntosh et al [108] detected expression of hBD-4 in cultured ocular surface cells, this defensin was found only infrequently in non-cultured samples.…”

Section: Amps Present At the Ocular Surfacementioning

confidence: 98%

“…Corneal and conjunctival epithelial cells also express hBD-3 [100,101,108] , but while some studies have indicated that expression of this defensin is inducible by TNF-␣ and interferon-␥ [42,43,109] , this was not observed in ocular surface epithelial cells [101] . Whilst McIntosh et al [108] detected expression of hBD-4 in cultured ocular surface cells, this defensin was found only infrequently in non-cultured samples. Huang et al [110] did not detect hBD-4, -5 or -6 in ocular surface cells.…”

Section: Amps Present At the Ocular Surfacementioning

confidence: 98%

The Role of Antimicrobial Peptides at the Ocular Surface

McDermott¹

2008

Ophthalmic Res

114

107

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Antimicrobial peptides (AMPs) such as defensins and cathelicidins are small peptides with broad-spectrum activity against bacteria, fungi and viruses. In addition, several AMPs modulate mammalian cell behaviours including migration, proliferation and cytokine production. This review describes findings from recent studies showing the presence of various AMPs at the human ocular surface and discusses their mechanism of antimicrobial action and potential non-microbicidal roles. Corneal and conjunctival epithelial cells produce β-defensins and the cathelicidin LL-37, whereas neutrophils, infiltrating in response to a specific stimulus, supply additional LL-37 as well as α-defensins. In vitro studies suggest that LL-37 and human β-defensin-3 are the most likely to have significant independent antimicrobial activity, while other AMPs may act synergistically to help protect the ocular surface from invading pathogens. Current evidence also supports a role for some AMPs in modulating wound healing responses. Although yet to be brought to fruition, AMPs hold significant potential as therapeutic agents for the prophylaxis and treatment of infection, promotion of wound healing and immune modulation.

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“…This hBD-2 upregulation in response to Pseudomonas aeruginosa might be reduced by the tyrosine kinase inhibitor, but the mechanisms of Pseudomonas aeruginosa-mediated upregulation are not fully understood. Lipopolysaccharide of Pseudomonas aeruginosa is involved in hBD-2 mRNA upregulation in the corneal epithelial cells [14,15]. The upregulation of defensins in the cornea in response to Pseudomonas aeruginosa has also been reported.…”

Section: Introductionmentioning

confidence: 90%