Frontiers in Immunology
·
2021
·
IF 7.561
Wu Binxin,Gao Furong,Lin Jianhua,Lu Lixia,Xu Huiming,Xu Guo-Tong
Allergic conjunctivitis (AC) is the most prevalent form of mucosal allergy, and the conditioned medium (CM) from mesenchymal stem cells has been reported to attenuate some allergic diseases. However, the therapeutic effects of CM from different tissue stem cells (TSC-CM) on allergic diseases have not been tested. Here, we studied the effects of topical administration of different human TSC-CM on experimental AC (EAC) mice. Only human amniotic epithelial cell-CM (AECM) significantly attenuated allergic eye symptoms and reduced the infiltration of immune cells and the levels of local inflammatory factors in the conjunctiva compared to EAC mice. In addition, AECM treatment decreased immunoglobulin E (IgE) release, histamine production, and the hyperpermeability of conjunctival vessels. Protein chip assays revealed that the levels of anti-inflammatory factors, interleukin-1 receptor antagonist (IL-1ra) and IL-10, were higher in AECM compared to other TSC-CM. Furthermore, the anti-allergic effects of AECM on EAC mice were abrogated when neutralized with IL-1ra or IL-10 antibody, and the similar phenomenon was for the activation and function of B cells and mast cells. Together, the present study demonstrated that AECM alleviates EAC symptoms by multiple anti-allergic mechanisms mainly via IL-1ra and IL-10. Such topical AECM therapy may represent a novel and feasible strategy for treating AC.
研究领域:
眼科学
·
免疫学
·
干细胞治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
·
2019
·
IF 4.708
Jin Cao,Jin Cheng,Siyu Xi,Xueyong Qi,Song Shen,Yanru Ge
Targeted delivery of bioactive compounds such as proteins to the colon has numerous advantages for the therapeutic treatment of inflammatory bowel disease . The present study sought to fabricate alginate/chitosan microcapsules containing IL-1Ra (Alg/Chi/IL-1Ra MC) via a single-step electrospraying method. Two important factors of efficacy were measured—the pH-responsiveness of the microcapsule and the in-vitro drug release profile. The DSS-induced colitis mouse model was used to evaluate the therapeutic effect of the Alg/Chi/IL-1Ra microcapsules, with results showing the protective effect of the Alg/Chi microcapsules for the passage of IL-1Ra through the harsh environment of the upper gastrointestinal tract . This effect was owing to the pH-sensitive response of the microcapsule, which allowed the targeted release of IL-1Ra in the colon. DAI evaluation, colon length, colon tissue morphology, histologic damage scores and relative protein concentrations (MPO, TNF-α and IL-1β) demonstrated that the Alg/Chi/IL-1Ra microcapsules alleviated DSS-induced colitis in mice. The present study thus demonstrates a practical means of oral delivery of proteins, in-situ colon release, and a promising application of IL-1Ra in the treatment of autoimmune and inflammatory diseases .
研究领域:
药学
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生物医学工程
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胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2024
·
IF 9.4
Youzhi Hong,Yudong Duan,Zhuang Zhu,Qifan Yu,Zhanfeng Mo,Huan Wang,Tao Zhou,Zhao Liu,Jianzhong Bai,Xiaoyu Zhang,Huilin Yang,Caihong Zhu,Bin Li
Presently, the clinical treatment of intervertebral disc degeneration (IVDD) remains challenging, but the strategy of simultaneously overcoming the overactive inflammation and restoring the anabolic/catabolic balance of the extracellular matrix (ECM) in the nucleus pulposus (NP) has become an effective way to alleviate IVDD. IL-1ra, a natural antagonist against IL-1β, can mitigate inflammation and promote regeneration in IVDD. Chondroitin sulfate (CS), an important component of the NP, can promote ECM synthesis and delay IVDD. Thus, these were chosen and integrated into functionalized microspheres to achieve their synergistic effects. First, CS-functionalized microspheres (GelMA-CS) with porous microstructure, good monodispersion, and about 200 µm diameter were efficiently and productively fabricated using microfluidic technology. After lyophilization, the microspheres with good local injection and tissue retention served as the loading platform for IL-1ra and achieved sustained release. In in vitro experiments, the IL-1ra-loaded microspheres exhibited good cytocompatibility and efficacy in inhibiting the inflammatory response of NP cells induced by lipopolysaccharide (LPS) and promoting the secretion of ECM. In in vivo experiments, the microspheres showed good histocompatibility, and local, minimally invasive injection of the IL-1ra-loaded microspheres could reduce inflammation, maintain the height of the intervertebral disc (IVD) and the water content of NP close to about 70 % in the sham group, and retain the integrated IVD structure. In summary, the GelMA-CS microspheres served as an effective loading platform for IL-1ra, eliminated inflammation through the controlled release of IL-1ra, and promoted ECM synthesis via CS to delay IVDD, thereby providing a promising intervention strategy for IVDD. Statement of significance The strategy of simultaneously overcoming the overactive inflammation and restoring the anabolic/catabolic balance of the extracellular matrix (ECM) in nucleus pulposus (NP) has shown great potential prospects for alleviating intervertebral disc degeneration (IVDD). From the perspective of clinical translation, this study developed chondroitin sulfate functionalized microspheres to act as the effective delivery platform of IL-1ra, a natural antagonist of interleukin-1β. The IL-1ra loading microspheres (GelMA-CS-IL-1ra) showed good biocompatibility , good injection with tissue retention, and synergistic effects of inhibiting the inflammatory response induced by lipopolysaccharide and promoting the secretion of ECM in NPCs. In vivo , they also showed the beneficial effect of reducing the inflammatory response, maintaining the height of the intervertebral disc and the water content of the NP, and preserving the integrity of the intervertebral disc structure after only one injection. All demonstrated that the GelMA-CS-IL-1ra microspheres would have great promise for the minimally invasive treatment of IVDD.
研究领域:
生物医学工程
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再生医学
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骨科研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACTA PHARMACOLOGICA SINICA
·
2020
·Vol. 42
·期 6
·987-997
·
IF 5.064
Liu Qiu-yan,Zhuang Yu,Song Xian-rui,Niu Qun,Sun Qiu-shuang,Li Xiao-nan,Li Ning,Liu Bao-lin,Huang Fang,Qiu Zhi-xia
Metabolic reprogramming is associated with NLRP3 inflammasome activation in activated macrophages, contributing to inflammatory responses. Tanshinone IIA (Tan-IIA) is a major constituent from Salvia miltiorrhiza Bunge, which exhibits anti-inflammatory activity. In this study, we investigated the effects of Tan-IIA on inflammation in macrophages in focus on its regulation of metabolism and redox state. In lipopolysaccharides (LPS)-stimulated mouse bone marrow-derived macrophages (BMDMs), Tan-IIA (10 μM) significantly decreased succinate-boosted IL-1β and IL-6 production, accompanied by upregulation of IL-1RA and IL-10 release via inhibiting succinate dehydrogenase (SDH). Tan-IIA concentration dependently inhibited SDH activity with an estimated IC 50 of 4.47 μM in LPS-activated BMDMs. Tan-IIA decreased succinate accumulation, suppressed mitochondrial reactive oxygen species production, thus preventing hypoxia-inducible factor-1α (HIF-1α) induction. Consequently, Tan-IIA reduced glycolysis and protected the activity of Sirtuin2 (Sirt2), an NAD + -dependent protein deacetylase, by raising the ratio of NAD + /NADH in activated macrophages. The acetylation of α-tubulin was required for the assembly of NLRP3 inflammasome; Tan-IIA increased the binding of Sirt2 to α-tubulin, and thus reduced the acetylation of α-tubulin, thus impairing this process. Sirt2 knockdown or application of Sirt2 inhibitor AGK-2 (10 μM) neutralized the effects of Tan-IIA, suggesting that Tan-IIA inactivated NLRP3 inflammasome in a manner dependent on Sirt2 regulation. The anti-inflammatory effects of Tan-IIA were observed in mice subjected to LPS challenge: pre-administration of Tan-IIA (20 mg/kg, ip) significantly attenuated LPS-induced acute inflammatory responses, characterized by elevated IL-1β but reduced IL-10 levels in serum. The peritoneal macrophages isolated from the mice displayed similar metabolic regulation. In conclusion, Tan-IIA reduces HIF-1α induction via SDH inactivation, and preserves Sirt2 activity via downregulation of glycolysis, contributing to suppression of NLRP3 inflammasome activation. This study provides a new insight into the anti-inflammatory action of Tan-IIA from the respect of metabolic and redox regulation.
研究领域:
免疫学
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药理学
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细胞代谢
·
炎症
·
氧化还原生物学
✓ 已验证
DOI
PubMed
高影响因子
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