The Role of Elastase in Corneal Epithelial Barrier Dysfunction Caused by <i>Pseudomonas aeruginosa</i> Exoproteins

Li, Ye; Wang, Yingwei; Li, Chunwei; Zhao, Depeng; Hu, QinYuan; Zhou, Min; Du, Miao; Li, Jian; Park, Wan

doi:10.1167/iovs.62.9.7

Cited by 5 publications

(5 citation statements)

References 32 publications

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“…Little is known about the function of AI-2 in modulating the behaviors of the host. Pyocyanin, which is a virulence factor of P. aeruginosa , can increase TGF-β1 secretion (Wang et al, 2021 ), while elastase, which is another virulence factor of P. aeruginosa , can increase IL-6 secretion (Li et al, 2021 ). Both TGF-β and IL-6 are crucial cytokines in the differentiation of CD4+ T cells into Th17 cells.…”

Section: Discussionmentioning

confidence: 99%

Autoinducer-2 promotes Pseudomonas aeruginosa PAO1 acute lung infection via the IL-17A pathway

et al. 2022

Front. Microbiol.

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Pseudomonas aeruginosa is an opportunistic pathogenic bacterium that causes various acute and chronic lung infections in immunocompromised patients. We previously found that a quorum sensing (QS) signal, namely, autoinducer-2 (AI-2), facilitates the pathogenicity of the wild-type (WT) P. aeruginosa PAO1 strain in vitro and in vivo. However, the immunological mechanism that leads to pulmonary injury remains to be elucidated. In this study, we aimed to investigate the effects of AI-2 on interleukin-17A (IL-17A) production during acute P. aeruginosa PAO1 lung infection using a mouse model, with an emphasis on the underlying immunological mechanism. Compared to infection with P. aeruginosa PAO1 alone, infection with P. aeruginosa PAO1 combined with AI-2 treatment resulted in significantly increased levels of IL-17A, numbers of Th17 cells and levels of STAT3 in the lung tissues of WT mice (P < 0.05), as well as more serious lung damage. In contrast, the concentrations of the proinflammatory cytokines IL-1α, IL-1β, and IL-6 and the chemokine keratinocyte-derived chemokine (KC) were significantly reduced during P. aeruginosa lung infection in IL-17A−/− mice compared with WT mice (P < 0.05), and no effects were observed after AI-2 treatment (P > 0.05). Furthermore, the level of IL-17A in the lungs of WT mice was significantly reduced following infection with a P. aeruginosa strain harboring mutations in the QS genes lasR and rhlR compared with the level of IL-17A following infection with P. aeruginosa PAO1. Our data suggest that AI-2 promotes P. aeruginosa PAO1 acute lung infection via the IL-17A pathway by interfering with the QS systems of P. aeruginosa. IL-17A may be a therapeutic target for the treatment of acute P. aeruginosa lung infections in the clinic.

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Section: Discussionmentioning

confidence: 99%

Autoinducer-2 promotes Pseudomonas aeruginosa PAO1 acute lung infection via the IL-17A pathway

et al. 2022

Front. Microbiol.

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“…Transepithelial electrical resistance (TEER) was measured using an EVOM voltameter (World Precision Instruments) to examine the integrity of the corneal epithelial barrier [4,25] . After 48h of growth on a 0.4 μm filter in 24-transwell plates with SHEM as well as another 24h of growth in unsupplemented DMEM-F12, the HCEs were exposed to 0, 125, 250, or 500 ng/mL Sema7A for 72h.…”

Section: Measurement Of Transepithelial Electrical Resistancementioning

confidence: 99%

“…The paracellular permeability of corneal epithelia was evaluated by the flow of 4 kDa Dextran-FITC, as previously reported [4,[25][26] . Briefly, after cells were exposed to 0, 125, 250, or 500 ng/mL Sema7A for 72h, a 2-hour incubation with 200 μL Dextran-FITC (3 mg/mL) in the apical chamber at the temperature of 37℃ was performed.…”

Section: Dextran-fluorescein Isothiocyanate Permeability Assaymentioning

confidence: 99%

“…T he corneal epithelium is a protective barrier between the outside world and the eyes [1][2] . The epithelial barrier and its integrity are essential for corneal homeostasis and resistant to environmental contaminants [3][4] . Disruptions in the epithelial barrier function and increased permeability have been associated with various eye disorders [1,4] , including diabetic keratopathy [5][6] and dry eye disease [7] .…”

Section: Introductionmentioning

confidence: 99%

“…The epithelial barrier and its integrity are essential for corneal homeostasis and resistant to environmental contaminants [3][4] . Disruptions in the epithelial barrier function and increased permeability have been associated with various eye disorders [1,4] , including diabetic keratopathy [5][6] and dry eye disease [7] . Human corneal epithelial cells (HCEs) exert their protective effect on eyes by through their barrier function, which is largely regulated by tight junctions (TJs) [8] .…”

Section: Introductionmentioning

confidence: 99%

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Semaphorin 7A impairs barrier function in cultured human corneal epithelial cells in a manner dependent on nuclear factor-kappa B

Yang,

Zhao,

Wang

et al. 2024

Int J Ophthalmol

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AIM: To evaluate the role of semaphorin 7A (Sema7A) and its associated regulatory mechanisms in modulating the barrier function of cultured human corneal epithelial cells (HCEs). METHODS: Barrier models of HCEs were treated with recombinant human Sema7A at concentrations of 0, 125, 250, or 500 ng/mL for 24, 48, or 72h in vitro. Transepithelial electrical resistance (TEER) as well as Dextran-fluorescein isothiocyanate (FITC) permeability assays were conducted to assess barrier function. To quantify tight junctions (TJs) such as occludin and zonula occludens-1 (ZO-1) at the mRNA level, reverse transcription-polymerase chain reaction (RT-PCR) analysis was performed. Immunoblotting was used to examine the activity of the nuclear factor-kappa B (NF-κB) signaling pathway and the production of TJs proteins. Immunofluorescence analyses were employed to localize the TJs. Enzyme-linked immunosorbent assay (ELISA) and RT-PCR were utilized to observe changes in interleukin (IL)-1β levels. To investigate the role of NF-κB signaling activation and IL-1β in Sema7A’s anti-barrier mechanism, we employed 0.1 µmol/L IκB kinase 2 (IKK2) inhibitor IV or 500 ng/mL IL-1 receptor (IL-1R) antagonist. RESULTS: Treatment with Sema7A resulted in decreased TEER and increased permeability of Dextran-FITC in HCEs through down-regulating mRNA and protein levels of TJs in a time- and dose-dependent manner, as well as altering the localization of TJs. Furthermore, Sema7A stimulated the activation of inhibitor of kappa B alpha (IκBα) and expression of IL-1β. The anti-barrier function of Sema7A was significantly suppressed by treatment with IKK2 inhibitor IV or IL-1R antagonists. CONCLUSION: Sema7A disrupts barrier function through its influence on NF-κB-mediated expression of TJ proteins, as well as the expression of IL-1β. These findings suggest that Sema7A could be a potential therapeutic target for the diseases in corneal epithelium.

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Bacterial zinc proteases

Capasso,

Supuran

2024

Metalloenzymes

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The Role of Elastase in Corneal Epithelial Barrier Dysfunction Caused by Pseudomonas aeruginosa Exoproteins

Cited by 5 publications

References 32 publications

Autoinducer-2 promotes Pseudomonas aeruginosa PAO1 acute lung infection via the IL-17A pathway

Autoinducer-2 promotes Pseudomonas aeruginosa PAO1 acute lung infection via the IL-17A pathway

Semaphorin 7A impairs barrier function in cultured human corneal epithelial cells in a manner dependent on nuclear factor-kappa B

Bacterial zinc proteases

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