Antimicrobial peptides expression by ocular surface cells in response to Acanthamoeba castellanii: an in vitro study

Otri, Ahmad Muneer; Mohammed, Imran; Abedin, A; Cao, Zhiyi; Hopkinson, Andrew; Panjwani, Noorjahan; Dua, Harminder S.

doi:10.1136/bjo.2009.178236

Cited by 31 publications

(29 citation statements)

References 40 publications

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“…RNase7 has been shown to target the outer membrane protein I of Pseudomonas aeruginosa 19. In addition to its protective role in human skin, RNase7 expression was recently shown to be increased in human corneal limbal epithelial cells stimulated with Acanthamoeba castellanii 20.…”

Section: Discussionmentioning

confidence: 99%

Modulation of epithelial immunity by mucosal fluid

Mun

Tam

Evans

et al. 2011

Sci Rep

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Mucosal epithelial cells, including those at the ocular surface, resist infection by most microbes in vivo but can be susceptible to microbial virulence in vitro. While fluids bathing mucosal surfaces (e.g. tears) contain antimicrobials, potentially pathogenic microbes often thrive in these fluids, suggesting that additional mechanisms mediate epithelial resistance in vivo. Here, tear fluid acted directly upon epithelial cells to enhance their resistance to bacterial invasion and cytotoxicity. Resistance correlated with tear fluid-magnified activation of NFκB and AP-1 transcription factors in epithelial cells in response to bacterial antigens, suggesting priming of innate defense pathways. Further analysis revealed differential regulation of potential epithelial cell defense genes by tears. siRNA knockdown confirmed involvement of at least two factors, RNase7 and ST-2, for which tears increased mRNA levels, in protection against bacterial invasion. Thus, the role of mucosal fluids in defense can include modulation of epithelial immunity, in addition to direct effects on microbes.

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Section: Discussionmentioning

confidence: 99%

Modulation of epithelial immunity by mucosal fluid

Mun

Tam

Evans

et al. 2011

Sci Rep

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“…Keratinocytes are the major source of this secreted innate defense protein in human skin [10]. RNase7 has been shown to be present in other epithelia in different organ systems including the respiratory, urinary and gastrointestinal tracts, and the eye (cornea) [10]–[13]. While RNase7 is constitutively expressed in these tissues, it can also be upregulated in response to various stimuli including proinflammatory cytokines (e.g.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-762 Is Upregulated in Human Corneal Epithelial Cells in Response to Tear Fluid and Pseudomonas aeruginosa Antigens and Negatively Regulates the Expression of Host Defense Genes Encoding RNase7 and ST2

et al. 2013

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Mucosal surfaces regulate defenses against infection and excessive inflammation. We previously showed that human tears upregulated epithelial expression of genes encoding RNase7 and ST2, which inhibited Pseudomonas aeruginosa invasion of human corneal epithelial cells. Here, microRNA microarrays were used to show that a combination of tear fluid exposure (16 h) then P. aeruginosa antigens (3 h) upregulated miR-762 and miR-1207, and down-regulated miR-92 and let-7b (all > 2-fold) in human corneal epithelial cells compared to P. aeruginosa antigens alone. RT-PCR confirmed miR-762 upregulation ∼ 3-fold in tear-antigen exposed cells. Without tears or antigens, an antagomir reduced miR-762 expression relative to scrambled controls by ∼50%, increased expression of genes encoding RNase7 (∼80 %), ST2 (∼58%) and Rab5a (∼75%), without affecting P. aeruginosa internalization. However, P. aeruginosa invasion was increased > 3-fold by a miR-762 mimic which reduced RNase7 and ST2 gene expression. Tear fluid alone also induced miR-762 expression ∼ 4-fold, which was reduced by the miR-762 antagomir. Combination of tear fluid and miR-762 antagomir increased RNase7 and ST2 gene expression. These data show that mucosal fluids, such as tears, can modulate epithelial microRNA expression to regulate innate defense genes, and that miR-762 negatively regulates RNase7, ST2 and Rab5a genes. Since RNase7 and ST2 inhibit P. aeruginosa internalization, and are upregulated by tear fluid, other tear-induced mechanisms must counteract inhibitory effects of miR-762 to regulate resistance to bacteria. These data also suggest a complex relationship between tear induction of miR-762, its modulation of innate defense genes, and P. aeruginosa internalization.

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“…More recently Otri et al . have observed that A. castellanii stimulated the expression of several HDPs including hBD-3 and LL-37 in cultured corneo-limbal epithelial cells but decreased expression of hBD-1 [88]. Together these studies suggest that HDPs may play a role in the innate response to Acanthamoeba keratitis but this needs to be investigated further.…”

Section: Role For Endogenous Host-defence Peptides In Eye Diseasesmentioning

confidence: 99%

Role of host-defence peptides in eye diseases

Kolar

McDermott

2011

Cell. Mol. Life Sci.

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The eye and its associated tissues including the lacrimal system and lids have evolved several defence mechanisms to prevent microbial invasion. Included among this armory are several host-defence peptides. These multifunctional molecules are being studied not only for their endogenous antimicrobial properties but also for their potential therapeutic effects. Here the current knowledge of host-defence peptide expression in the eye will be summarized. The role of these peptides in eye disease will be discussed with the primary focus being on infectious keratitis, inflammatory conditions including dry eye and wound healing. Finally the potential of using host-defence peptides and their mimetics/derivatives for the treatment and prevention of eye diseases is addressed.

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Antimicrobial peptides expression by ocular surface cells in response to Acanthamoeba castellanii: an in vitro study

Cited by 31 publications

References 40 publications

Modulation of epithelial immunity by mucosal fluid

Modulation of epithelial immunity by mucosal fluid

MicroRNA-762 Is Upregulated in Human Corneal Epithelial Cells in Response to Tear Fluid and Pseudomonas aeruginosa Antigens and Negatively Regulates the Expression of Host Defense Genes Encoding RNase7 and ST2

Role of host-defence peptides in eye diseases

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