Cyclosporin H is a potent and selective formyl peptide receptor (FPR) antagonist with an IC50 value of 0.7μM[1]. Cyclosporin H can be used as a viral transduction enhancer to improve the efficiency of lentiviral transduction in hematopoietic stem cells and progenitor cells [2].
In vitro, Cyclosporin H (1 μM) treated A549 cells for 30 min and strongly inhibited mitochondrial DAMP-induced IL-8 release in cells [1]. Cyclosporin H (8μM) treated mouse hematopoietic progenitor cells and stem cells for 24 hours, significantly improving the efficiency of cellular lentiviral transduction [3]. Cyclosporin H (8-800 nM) treats N-formyl-methionine-leucine-phenylalanine (FMLP)-activated basophils and concentration-dependently inhibits the release of histamine and leukotriene C4 from cells[4].
In vivo, Cyclosporin H (2mg/kg) treated lung injury model mice through intravenous injection, reduced the entry of neutrophils into the alveolar space, inhibited the levels of inflammatory factors in the bronchoalveolar lavage fluid, and improved lung morphological damage [5]. Cyclosporin H (30mg/kg) treated middle cerebral artery occlusion (MCAO) model mice through intravenous injection, alleviated ischemic cerebral infarction and inhibited neutrophil infiltration [6]. Cyclosporin H (30 mg/kg), administered intraperitoneally to breast cancer mice, produced an immunosuppressive effect and reduced the efficacy of chemotherapy with mitoxantrone (MTX) and cyclophosphamide (CTX) [7].
References:
[1] Wenzel-Seifert K, Seifert R. Cyclosporin H is a potent and selective formyl peptide receptor antagonist. Comparison with Nt-butoxycarbonyl-L-phenylalanyl-L-leucyl-L-phenylalanyl-L-leucyl-L-phenylalanine and cyclosporins A, B, C, D, and E[J]. Journal of immunology, 1993, 150: 4591-4599.
[2] Petrillo C, Thorne L G, Unali G, et al. Cyclosporine H overcomes innate immune restrictions to improve lentiviral transduction and gene editing in human hematopoietic stem cells[J]. Cell Stem Cell, 2018, 23(6): 820-832. e9.
[3] Olender L, Bujanover N, Sharabi O, et al. Cyclosporine H improves the multi-vector lentiviral transduction of murine haematopoietic progenitors and stem cells[J]. Scientific Reports, 2020, 10(1): 1812.
[4] de Paulis A, Ciccarelli A, de Crescenzo G, et al. Cyclosporin H is a potent and selective competitive antagonist of human basophil activation by N-formyl-methionyl-leucyl-phenylalanine[J]. Journal of allergy and clinical immunology, 1996, 98(1): 152-164.
[5] Zhang X, Wang T, Yuan Z C, et al. Mitochondrial peptides cause proinflammatory responses in the alveolar epithelium via FPR-1, MAPKs, and AKT: a potential mechanism involved in acute lung injury[J]. American Journal of Physiology-Lung Cellular and Molecular Physiology, 2018, 315(5): L775-L786.
[6] Hong Z, Xu H, Ni K, et al. Effect of Cyclosporin H on ischemic injury and neutrophil infiltration in cerebral infarct model of rats via PET imaging[J]. Annals of Nuclear Medicine, 2024: 1-13.
[7] Baracco E E, Pietrocola F, Buqué A, et al. Inhibition of formyl peptide receptor 1 reduces the efficacy of anticancer chemotherapy against carcinogen-induced breast cancer[J]. Oncoimmunology, 2016, 5(6): e1139275.
环孢菌素H（Cyclosporin H）是一种有效的选择性甲酰基肽受体（FPR）拮抗剂，IC50值为0.7μM[1]。Cyclosporin H可作为一种病毒转导增强剂，提高造血干细胞和祖细胞中慢病毒转导效率[2]。
在体外，Cyclosporin H（1μM）处理A549细胞30min，强烈抑制了线粒体DAMP诱导的细胞中IL-8的释放[1]。Cyclosporin H（8μM）处理小鼠造血祖细胞和干细胞24h，显著提高了细胞慢病毒转导效率[3]。Cyclosporin H（8-800 nM）处理N-甲酰-蛋氨酸-亮氨酸-苯丙氨酸（FMLP）激活后的嗜碱性粒细胞，浓度依赖性地抑制细胞释放组胺和白三烯C4[4]。
在体内，Cyclosporin H（2mg/kg）通过静脉注射治疗肺损伤模型小鼠，减少了中性粒细胞进入肺泡腔，抑制了支气管肺泡灌洗液中的炎症因子水平，改善了肺形态损伤[5]。Cyclosporin H（30mg/kg）通过静脉注射治疗大脑中动脉闭塞（MCAO）模型小鼠，缓解了缺血性脑梗死，抑制了中性粒细胞浸润[6]。Cyclosporin H（30mg/kg）通过腹膜内注射治疗乳腺癌小鼠，产生了免疫抑制作用，降低了米托蒽醌（MTX）和环磷酰胺（CTX）进行化疗的功效[7]。