A Novel Antimicrobial Peptide on the Ocular Surface Shows Decreased Expression in Inflammation and Infection

Abedin, A; Mohammed, Imran; Hopkinson, Andrew; Dua, Harminder S.

doi:10.1167/iovs.07-0645

Cited by 35 publications

(42 citation statements)

References 37 publications

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“…6). This complements our previous studies [1,2,17,18] and those of others [19,20] in relation to defensin and cathelicidin families at the OS.…”

Section: Discussionsupporting

confidence: 90%

Signalling pathways involved in ribonuclease-7 expression

Mohammed¹,

Yeung²,

Abedin³

et al. 2010

Cell. Mol. Life Sci.

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Antimicrobial peptides are host defence molecules that play a potential role in preventing infection at the epithelial surfaces. Ribonuclease (RNase)-7 has been shown to possess a broad spectrum of microbicidal activity against various pathogens. Here, we demonstrate that RNase-7 protein is localised to the superficial layers of ocular surface cells and increased in response to interleukin (IL)-1β, suggesting an active role during inflammation related to ocular surface infection. Signal transduction pathways involved in RNase-7 expression are unknown. Involvement of transforming growth factor β-activated kinase-1 (TAK-1) activated nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathway molecules [c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and p38] were studied because of their importance in infection and inflammation. Blocking the MAPKs resulted in inhibition of RNase-7 expression in response to IL-1β. However, RNase-7 induction by IL-1β was not affected by inhibiting the NF-κB signalling pathway. In conclusion, our results indicate that RNase-7 expression is specifically mediated via MAPKs but not NF-κB signalling pathways.

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“…6). This complements our previous studies [1,2,17,18] and those of others [19,20] in relation to defensin and cathelicidin families at the OS.…”

Section: Discussionsupporting

confidence: 90%

Signalling pathways involved in ribonuclease-7 expression

Mohammed¹,

Yeung²,

Abedin³

et al. 2010

Cell. Mol. Life Sci.

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“…McIntosh et al [108] also studied the expression of 13 putative novel ␤ -defensin genes (DEFB105, 107, 108, 118-123, 125-127, 129) in ocular surface tissue but did not find them to be present. In a recent study, expression of a novel ␤ -defensin gene, DEFB109, was detected in the ocular surface epithelia, and interestingly its expression was decreased in inflammation and infection [111] . It should also be noted that in contrast to the ␣ -defensins, ␤ -defensins have not been detected in the tear film [95,112] .…”

Section: Amps Present At the Ocular Surfacementioning

confidence: 97%

The Role of Antimicrobial Peptides at the Ocular Surface

McDermott¹

2008

Ophthalmic Res

113

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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“…On the other hand, Li et al (2009) demonstrated that hBD2 and -3 selectively increase the secretion of speciWc proinXammatory cytokines in conjunctival epithelial cells in a time-and concentration-dependent manner suggesting a supporting role to the innate immune system of the ocular surface. Finally, it should be mentioned that in a recent study, the group of Dua et al (Abedin et al 2008) detected the expression of a novel -defensin, DEFB-109, which was detected in ocular surface epithelia and unexpectedly showed decreased expression during inXammation and infection.…”

Section: Introductionmentioning

confidence: 96%

Roles of human β-defensins in innate immune defense at the ocular surface: arming and alarming corneal and conjunctival epithelial cells

Garreis

Schlorf

Worlitzsch

et al. 2010

Histochem Cell Biol

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Human beta-defensins are cationic peptides produced by epithelial cells that have been proposed to be an important component of immune function at mucosal surfaces. In this study, the expression and inducibility of beta-defensins at the ocular surface were investigated in vitro and in vivo. Expression of human beta-defensins (hBD) was determined by RT-PCR and immunohistochemistry in tissues of the ocular surface and lacrimal apparatus. Cultured corneal and conjunctival epithelial cells were stimulated with proinflammatory cytokines and supernatants of different ocular pathogens. Real-time PCR and ELISA experiments were performed to study the effect on the inducibility of hBD2 and 3. Expression and inducibility of mouse beta-defensins-2, -3 and -4 (mBD2-4) were tested in a mouse ocular surface scratch model with and without treatment of supernatants of a clinical Staphylococcus aureus (SA) isolate by means of immunohistochemistry. Here we show that hBD1, -2, -3 and -4 are constitutively expressed in conjunctival epithelial cells and also partly in cornea. Healthy tissues of the ocular surface, lacrimal apparatus and human tears contain measurable amounts of hBD2 and -3, with highest concentrations in cornea and much lower concentrations in all other tissues, especially tears, suggesting intraepithelial storage of beta-defensins. Exposure of cultured human corneal and conjunctival epithelial cells to proinflammatory cytokines and supernatants of various bacteria revealed that IL-1beta is a very strong inductor of hBD2 and Staphylococcus aureus increases both hBD2 and hBD3 production in corneal and conjunctival epithelial cells. A murine corneal scratch model demonstrated that beta-defensins are only induced if microbial products within the tear film come into contact with a defective epithelium. Our finding suggests that the tear film per se contains so much antimicrobial substances that epithelial induction of beta-defensins occurs only as a result of ocular surface damage. These findings widen our knowledge of the distribution, amount and inducibility of beta-defensins at the ocular surface and lacrimal apparatus and show how beta-defensins are regulated specifically.

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A Novel Antimicrobial Peptide on the Ocular Surface Shows Decreased Expression in Inflammation and Infection

Cited by 35 publications

References 37 publications

Signalling pathways involved in ribonuclease-7 expression

Signalling pathways involved in ribonuclease-7 expression

The Role of Antimicrobial Peptides at the Ocular Surface

Roles of human β-defensins in innate immune defense at the ocular surface: arming and alarming corneal and conjunctival epithelial cells

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