Resolvin E1 Inhibits Corneal Allograft Rejection in High-Risk Corneal Transplantation

Wang, Han; Zhao, Qingqing; Luo, Dan; Yin, Yizhou; Li, Ting; Zhao, Min

doi:10.1167/iovs.18-24562

Cited by 15 publications

(16 citation statements)

References 40 publications

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“…RvE1 exerts bioactivities of antiinflammation, pro-resolving, and tissue protection by binding to its protein-coupled receptor, ChemR23, on various cells, including monocytes, macrophages, dendritic cells, NK cells and endothelial cells (19). Specifically, RvE1 induces an antiinflammatory effect, both acutely and chronically, by blocking the production of proinflammatory cytokines (20), inhibiting neutrophil transendothelial migration (17) and enhancing phagocytosis of microbial particles and apoptotic neutrophils (21). Apart from inflammation mediation, RvE1 also functions protectively by accelerating the restoration of endothelium function (22), alleviating tissue damage (23) and promoting bone preservation (24).…”

Section: Introductionmentioning

confidence: 99%

Resolvin E1 in Follicular Fluid Acts as a Potential Biomarker and Improves Oocyte Developmental Competence by Optimizing Cumulus Cells

Zhang

Zhu

et al. 2020

Front. Endocrinol.

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Metabolic profile of follicular fluid (FF) has been investigated to look for biomarkers for oocyte quality. Resolvin E1 (RvE1), a potent pro-resolving mediator, was reported to have protective action in cell function. The study aimed to examine the predictive value of RvE1 for oocyte quality and to explore the cellular mechanism of RvE1 in improving oocyte competence. Metabolic profiles of 80 FF samples showed a higher level of RvE1 in group A (blastocysts scored ≥ B3BC and B3CB according to Gardner's blastocyst scoring system, N = 36) than that of group B (blastocysts scored < B3BC and B3CB, N = 44, P = 0.0018). The receiver operating characteristic (ROC) curve analysis showed that RvE1 level in FF below 8.96 pg/ml (AUC:0.75; 95%CI: 0.64-0.86; P = 0.00012) could predict poor oocyte quality with specificity of 97.22%, suggesting RvE1 as a potential biomarker to exclude inferior oocytes. Besides, the level of RvE1 was found to be significantly lower in FF than in serum (57.49 to 17.62 pg/ml; P = 0.0037) and was gradually accumulated in the culture medium of cumulus cells (CCs) during cell culture, which indicated that RvE1 came from both blood exudates and local secretion. The in vitro experiment revealed the cellular mechanism of RvE1 in improving oocyte quality by decreasing the cumulus cell apoptotic rate and increasing cell viability and proliferation. It is the first time that the role of RvE1 in reproduction is explored. In conclusion, RvE1 is valuable as a potential exclusive biomarker for oocyte selection and plays a role in improving oocyte quality.

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Section: Introductionmentioning

confidence: 99%

Resolvin E1 in Follicular Fluid Acts as a Potential Biomarker and Improves Oocyte Developmental Competence by Optimizing Cumulus Cells

Zhang

Zhu

et al. 2020

Front. Endocrinol.

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“…Our study is the first to compare multiple aspects of corneal rejection between M1- and M2-dominated immune response models, namely C57BL/6J and BALB/c mice. These mouse strains are two of the most widely used models for rejection studies [7-9, 12, 24, 25, 27, 44, 45]. The results of our study indicate that these studies deserve cautious interpretation.…”

Section: Discussionmentioning

confidence: 66%

Different Innate Immune Responses in BALB/c and C57BL/6 Strains following Corneal Transplantation

et al. 2020

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Purpose: To investigate immunological differences and the role of CD38+/F4/80 + M1 macrophages in C57BL/6J- and BALB/c-recipient mouse corneal transplantation models. Methods: Allogeneic transplantation was performed crosswise in BALB/c mice and C57BL/6J mice; syngeneic transplantation was performed in both strains. Anterior chamber depth (ACD) was measured before and central corneal thickness (CCT) was measured both before and after transplantation. In vivo graft rejection was monitored using anterior eye segment optical coherence tomography (ASOCT) evaluating the CCT and grading of corneal oedema using a well-established clinical score (CS). Histology of corneal grafts was performed 18 or 21 days after surgery. Immunohistochemistry with anti-F4/80 antibody and anti-CD38 antibody was used for detecting M1 macrophages within the grafts. Results: High CS and CCT values after allogeneic transplantation persisted in both BALB/c (n = 18) and C57BL/6J recipients (n = 20). After syngeneic transplantation, CS and CCT values increased in both models in the early phase after surgery due to the surgical trauma. Surprisingly, in the syngeneic C57BL/6J model, high CCT values persisted. Furthermore, anterior synechiae developed in C57BL/6 recipients after both syngeneic and allogeneic transplantation, whereas BALB/c recipients showed almost no synechiae – even though C57/BL6J animals tended to have a deeper anterior chamber (281 ± 11 pixels [mean ± SD]) compared with BALB/c animals of the same age (270 ± 9 pixels [mean ± SD]). Immunohistochemistry revealed numerous CD38+/F4/80 + M1 macrophages in grafts of C57BL/6J recipients following both syngeneic and allogeneic transplantation. However, in BALB/c-recipient mice only sparse M1 macrophages were detectable (CD38 + M1 macrophages relative to all F4/80 + cells: 75 vs. 17% [after allogeneic transplantation] and 66 vs. 17% [after syngeneic transplantation]; p < 0.05). Conclusions: Allogeneic corneal transplants are rejected in BALB/c as well as C57BL/6J mice, but tissue alterations with anterior synechiae are more pronounced in C57BL/6J recipients. Following syngeneic transplantation, C57BL/6J-recipient animals show a persistent graft swelling with increased numbers of CD38+/F4/80 + M1 macrophages in grafted tissue, in contrast to the common model using BALB/c-recipient mice. Our data strongly suggest that strain-dependent differences convey different innate immune responses in BALB/c and C57BL/6J strains. Accordingly, in murine keratoplasty experiments, the mouse line of both donor and recipient animals must be carefully considered. C57BL/6J-recipient mice might be particularly suited to study corneal graft rejection in a clinical setting considered “high risk.”

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“…Rey et al reported that RvE1 decreased LPSinduced gene expression of proin ammatory cytokines (TNF-α and IL-6), suggesting that they exerted proresolutive activity in microglia [29]. Wang et al reported that RvE1 treatment improved allogeneic corneal graft survival by signi cantly reducing the mRNA expression of proin ammatory cytokines, including TNF-α, IL-6 and IFN-γ, in corneal grafts, as well as the protein level of the proin ammatory cytokines TNF-α, IL-6 and IFN-γ [30]. However no similar ndings have been reported in the inner ear.…”

Section: Discussionmentioning

confidence: 99%

A unique radioprotective effect of resolvin E1 reduces irradiation-induced damage to the inner ear by inhibiting the inflammatory response

Zhang

Niu

et al. 2020

Preprint

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Background: In addition to the direct effects of irradiation, the induced inflammatory response may play an important role in the damage to the inner ear caused by radiotherapy for the treatment of head and neck cancers. Resolvin E1 (RvE1) has anti-inflammatory activity, acting by reducing neutrophil infiltration and proinflammatory cytokine expression. Therefore, in this study we sought to confirm whether the inflammation induced by irradiation was involved in damage to the inner ear after radiotherapy and to investigate the protective effect and underlying mechanism of RvE1 using mouse models. Methods: A dose of RvE1 was delivered by intraperitoneal injection to mice before irradiation. Changes in the auditory brainstem response (ABR), relative balance ability, inner ear morphology and the expression levels of inflammatory factors in the inner ear were analyzed on days 7 and 14 after irradiation and compared among different experimental groups. Results: Changes of ABR and relative balance ability showed the inner functions of experimental mice presented severe damage after irradiation, but the damage was significantly alleviated after RvE1 pretreatment compared to irradiation alone. Morphological analysis of the inner ear showed severe damage to the cochlea and vestibule after irradiation. In contrast, damage to the cochlea and vestibule was significantly reduced in the RvE1-pretreated group compared to that in the irradiation alone group. Along with these functional and morphological changes, the mRNA expression level of anti-inflammatory factors interleukin-2 was significantly increased, while those of proinflammatory factors interleukin-6 and tumor necrosis factor-α were significantly decreased in the inner ear of mice after RvE1 pretreatment compared to irradiation alone. Conclusions: We believe that inflammation induced by irradiation is involved in the damage to the inner ear caused by radiotherapy, and that RvE1 reduces the damage caused by irradiation to the inner ear by regulating the induced inflammatory response.

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Resolvin E1 Inhibits Corneal Allograft Rejection in High-Risk Corneal Transplantation

Abstract: RvE1 treatment improves allogeneic corneal graft survival in a high-risk corneal transplantation model via inhibiting the Th1/Th17-related inflammation.

Cited by 15 publications

References 40 publications

Resolvin E1 in Follicular Fluid Acts as a Potential Biomarker and Improves Oocyte Developmental Competence by Optimizing Cumulus Cells

Resolvin E1 in Follicular Fluid Acts as a Potential Biomarker and Improves Oocyte Developmental Competence by Optimizing Cumulus Cells

Different Innate Immune Responses in BALB/c and C57BL/6 Strains following Corneal Transplantation

A unique radioprotective effect of resolvin E1 reduces irradiation-induced damage to the inner ear by inhibiting the inflammatory response

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