Fenretinide Inhibits Neutrophil Recruitment and IL-1β Production in Aspergillus fumigatus Keratitis

Zhao, Wenyi; Che, Chengye; Liu, Kuixiang; Zhang, Jie; Jiang, Nan; Yuan, Kelan; Zhao, Guiqiu

doi:10.1097/ico.0000000000001756

Cited by 17 publications

(7 citation statements)

References 36 publications

(38 reference statements)

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“…IL-1β is an important inflammation mediator and a proinflammatory cytokine (Zhang et al, 2018), which is involved in multiple cellular activities such as cell proliferation, apoptosis, and differentiation (Zhao et al, 2018). IL-33 is a member of the IL-1 family and has been identified as a mediator of various inflammatory diseases such as asthma, cardiovascular diseases, and allergic diseases (Liew et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Association of TREM-1, IL-1β, IL-33/ST2, and TLR Expressions With the Pathogenesis of Ocular Toxoplasmosis in Mouse Models on Different Genetic Backgrounds

et al. 2019

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Ocular toxoplasmosis (OT) is one of the most common causes of posterior uveitis. The signaling of triggering receptor expressed on myeloid cells (TREM)-1 amplifies inflammation, whereas TREM-2 signaling is anti-inflammatory. IL-1β is a major driver of inflammation during infection. Toll-like receptors (TLRs) play important roles in protective immune response during Toxoplasma gondii infection, and interleukin (IL)-33 receptor (T1/ST2) signaling prevents toxoplasmic encephalitis in mice. However, the pathogenic mechanisms of OT are not yet well elucidated. To investigate the role of TREM-1, TREM-2, IL-1β, IL-33/ST2, and TLRs in OT of susceptible C57BL/6 (B6) and resistant BALB/c mice, both strains of mice were intravitreally infected with 500 tachyzoites of the RH strain of T. gondii. Histopathological analysis showed that T. gondii-infected B6 mice had more severe ocular damage observed by light microscopy, higher number of neutrophil elastase-positive cells in the eyes detected by immunohistochemical staining, more T. gondii tachyzoites in the eyes observed by transmission electron microscopy, and higher mRNA expression levels of tachyzoite-specific surface antigen 1 detected by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) in comparison of T. gondii-infected BALB/c mice. Detected by using qRT-PCR, the mRNA expression levels of TREM-1, IL-1β, IL-33, ST2, TLR11, TLR12, and TLR13 were significantly higher in the eyes of T. gondii-infected B6 mice than those of T. gondii-infected BALB/c mice, whereas the mRNA expression levels of TLR3 and TLR9 were significantly higher in the eyes of T. gondii-infected BALB/c mice than those of T. gondii-infected B6 mice. Correlation analysis showed that significant positive correlations existed between TREM-1 and IL-1β/IL-33/ST2/TLR9/TLR11 in the eyes of B6 mice and existed between TREM-1 and IL-33/ST2/TLR3/TLR9/TLR13 in the eyes of BALB/c mice after ocular T. gondii infection. Our data revealed that, compared with T. gondii-resistant BALB/c mice, ocular T. gondii infection can stimulate higher production of TREM-1, IL-33, ST2, TLR11, TLR12, and TLR13 in the eyes of T. gondii-susceptible B6 mice, however, whether those lead to more severe ocular pathology in the susceptible B6 mice remain to be further studied.

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Section: Introductionmentioning

confidence: 99%

Association of TREM-1, IL-1β, IL-33/ST2, and TLR Expressions With the Pathogenesis of Ocular Toxoplasmosis in Mouse Models on Different Genetic Backgrounds

et al. 2019

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“…are also involved in fungal keratitis, a major cause of corneal ulcers, resulting in significant visual impairment and blindness. Zhao et al [34] investigated the effect of fenretinide in Aspergillus fumigatus keratitis In vivo in a mouse model as well as In vitro in a THP-1-derived macrophage cell line infected with A. fumigatus. In both experimental models, the pretreatment with fenretinide contributed to protecting corneal transparency during A. fumigatus keratitis in the early phase of the infection by reducing neutrophil recruitment, decreasing myeloperoxidase (MPO) levels and increasing apoptosis.…”

Section: Effectiveness Of Retinoids Against Environmental Humanmentioning

confidence: 99%

“…In both experimental models, the pretreatment with fenretinide contributed to protecting corneal transparency during A. fumigatus keratitis in the early phase of the infection by reducing neutrophil recruitment, decreasing myeloperoxidase (MPO) levels and increasing apoptosis. Compared with controls, fenretinide also impaired proinflammatory cytokine interleukin 1 beta (IL-1β) production in response to A. fumigatus exposure through the blockade of the lectin-type oxidized LDL receptor 1 (LOX-1) and c-Jun N-terminal kinase (JNK) pathway [34]. All retinoids evaluated in Aspergillus spp.…”

Section: Effectiveness Of Retinoids Against Environmental Humanmentioning

confidence: 99%

Retinoids in Fungal Infections: From Bench to Bedside

et al. 2021

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Retinoids—a class of chemical compounds derived from vitamin A or chemically related to it—are used especially in dermatology, oncohematology and infectious diseases. It has been shown that retinoids—from their first generation—exert a potent antimicrobial activity against a wide range of pathogens, including bacteria, fungi and viruses. In this review, we summarize current evidence on retinoids’ efficacy as antifungal agents. Studies were identified by searching electronic databases (MEDLINE, EMBASE, PubMed, Cochrane, Trials.gov) and reference lists of respective articles from 1946 to today. Only articles published in the English language were included. A total of thirty-nine articles were found according to the criteria. In this regard, to date, In vitro and In vivo studies have demonstrated the efficacy of retinoids against a broad-spectrum of human opportunistic fungal pathogens, including yeast fungi that normally colonize the skin and mucosal surfaces of humans such as Candida spp., Rhodotorula mucilaginosa and Malassezia furfur, as well as environmental moulds such as Aspergillus spp., Fonsecae monofora and many species of dermatophytes associated with fungal infections both in humans and animals. Notwithstanding a lack of double-blind clinical trials, the efficacy, tolerability and safety profile of retinoids have been demonstrated against localized and systemic fungal infections.

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“…For example, cytokines can be detected at the protein level by ELISA, label-based protein assays, and Western blotting at the RNA level by PCR [32][33][34]36,40,46]. Myeloperoxidase (MPO) is highly abundant in neutrophil granulocytes and other immune cells, and its activity can be measured by commercially available kits; 1 unit of MPO activity corresponds to approximately 2.0 × 10 5 PMNs [36,40,59]. The release of metalloproteases, which mediate the destruction of the corneal extracellular matrix during infection, can easily be assayed by zymography [43].…”

Section: Disease Assessmentmentioning

confidence: 99%

“…This study ultimately indicated that IL-17 expression, but not IFNγ expression, was associated with protective immunity following Aspergillus keratitis [ 58 ]. Zhao et al found that the subconjunctival injection of fenretinide, a synthetic vitamin A derivative that inhibits the activation of NFKβ’s (Nuclear factor kappa-light-chain-enhancer of activated B cells) proinflammatory signaling cascade, resulted in the protection of corneal transparency during an intrastromal model of Aspergillus keratitis utilizing 0.5 × 10 5 conidia/μL [ 59 ].…”

Section: In Vivo Modelsmentioning

confidence: 99%

Experimental Models for Fungal Keratitis: An Overview of Principles and Protocols

Montgomery

Fuller

2020

Cells

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Fungal keratitis is a potentially blinding infection of the cornea that afflicts diverse patient populations worldwide. The development of better treatment options requires a more thorough understanding of both microbial and host determinants of pathology, and a spectrum of experimental models have been developed toward this end. In vivo (animal) models most accurately capture complex pathological outcomes, but protocols may be challenging to implement and vary widely across research groups. In vitro models allow for the molecular dissection of specific host cell–fungal interactions, but they do so without the appropriate environmental/structural context; ex vivo (corneal explant) models provide the benefits of intact corneal tissue, but they do not provide certain pathological features, such as inflammation. In this review, we endeavor to outline the key features of these experimental models as well as describe key technical variations that could impact study design and outcomes.

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Fenretinide Inhibits Neutrophil Recruitment and IL-1β Production in Aspergillus fumigatus Keratitis

Cited by 17 publications

References 36 publications

Association of TREM-1, IL-1β, IL-33/ST2, and TLR Expressions With the Pathogenesis of Ocular Toxoplasmosis in Mouse Models on Different Genetic Backgrounds

Association of TREM-1, IL-1β, IL-33/ST2, and TLR Expressions With the Pathogenesis of Ocular Toxoplasmosis in Mouse Models on Different Genetic Backgrounds

Retinoids in Fungal Infections: From Bench to Bedside

Experimental Models for Fungal Keratitis: An Overview of Principles and Protocols

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