BPIFA1

更新于：2025-05-07

基本信息

别名

bA49G10.5、BPI fold containing family A member 1、BPI fold-containing family A member 1

+ [13]

简介

Lipid-binding protein which shows high specificity for the surfactant phospholipid dipalmitoylphosphatidylcholine (DPPC) (PubMed:25223608). Plays a role in the innate immune responses of the upper airways (PubMed:23132494, PubMed:23499554). Reduces the surface tension in secretions from airway epithelia and inhibits the formation of biofilm by pathogenic Gram-negative bacteria, such as P.aeruginosa and K.pneumoniae (PubMed:23132494, PubMed:23499554, PubMed:27145151). Negatively regulates proteolytic cleavage of SCNN1G, an event that is required for activation of the epithelial sodium channel (ENaC), and thereby contributes to airway surface liquid homeostasis and proper clearance of mucus (PubMed:24043776, PubMed:24124190). Plays a role in the airway inflammatory response after exposure to irritants (PubMed:11425234). May attract macrophages and neutrophils (PubMed:23132494).

关联

项与 BPIFA1 相关的药物

ELD-607

靶点

BPIFA1 x ORAI1

作用机制

BPIFA1 stimulators [+1]

在研机构

Eldec Pharmaceuticals, Inc.

原研机构

Eldec Pharmaceuticals, Inc.

在研适应症

肠杆菌感染 [+5]

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 BPIFA1 相关的临床结果

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100 项与 BPIFA1 相关的转化医学

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0 项与 BPIFA1 相关的专利（医药）

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287

项与 BPIFA1 相关的文献（医药）

2025-05-01·Archives of Oral Biology

BPIFA1 inhibits periodontitis by regulating the NF-κB/IκB signaling pathway and macrophage M1/M2 polarization

Article

作者: Xu, Hongyan ; Yang, Ying ; Wang, Tao

BACKGROUNDPeriodontitis is a chronic inflammatory disease characterized by tissue destruction and oxidative stress, primarily driven by the imbalance of immune responses. Bactericidal/permeability-increasing fold-containing family A member 1 (BPIFA1) has emerged as a key modulator of inflammation and immune homeostasis.OBJECTIVESThis study investigates the role of BPIFA1 in periodontitis by focusing on its regulatory effects on the NF-κB/IκB signaling pathway and macrophage M1/M2 polarization.METHODSSaliva and periodontal tissue samples were collected from 20 periodontitis patients and 20 healthy volunteers. BPIFA1 expression was analyzed using qRT-PCR and Western blot. In vivo studies were conducted in wild-type and BPIFA1-knockout (KO) mice, where periodontitis was induced via ligature placement and LPS injections. Oxidative stress markers (ROS, MDA, SOD), inflammatory cytokines (TNF-α, IL-6), and macrophage polarization markers (iNOS, CD86, Arg-1, CD206) were quantified. NF-κB pathway activation was assessed through Western blot analysis.RESULTSBPIFA1 expression was significantly reduced in periodontitis patients and BPIFA1-KO mice. Loss of BPIFA1 resulted in increased oxidative stress, heightened NF-κB activation, and an imbalance in macrophage polarization, with increased M1 (pro-inflammatory) and decreased M2 (anti-inflammatory) macrophages. Additionally, BPIFA1 deficiency promoted Th17 differentiation and suppressed Treg cells, exacerbating periodontal inflammation.CONCLUSIONBPIFA1 plays a critical role in inhibiting periodontitis progression by regulating the NF-κB/IκB signaling pathway and restoring macrophage M1/M2 balance. These findings highlight BPIFA1 as a potential therapeutic target for periodontitis management.

2025-03-01·Journal of Ethnopharmacology

Zhichuanling injection improves bronchial asthma by attenuation airway inflammation and epithelia-mesenchymal transition

Article

作者: Liang, Huaduan ; Cao, Zhengyu ; Song, Mengmeng ; Zhao, Fang ; Niu, Bo ; Chen, Jingyi ; Ren, Kerui ; Xi, Chuchu

ETHNOPHARMACOLOGICAL RELEVANCEZhichuanling (ZCL) Injection, is a compound formulation containing extracts of mahuang (Herba Ephedrae, dried stem or aerial part of Ephedra sinica Stapf), bitter almond (Semen Armeniacae Amarum, seeds of Prunus armeniaca var. sibirica (L.) K. Koch), yangjinhua (flower of Datura metel L.) and Fructus Forsythiae (fruits of Forsythia suspensa (Thunb.) Vahl). Intramuscular injection of ZCL has been used in the clinical practice to control asthma. The aerosol inhalation of ZCL has been shown to be effective on allergic bronchial asthma. However, the underlying mechanisms remain established.AIM OF THE STUDYTo investigate the underling mechanism by which ZCL inhibits the pathogenesis of bronchial asthma.METHODSThe guinea pig tracheal rings and human bronchial epithelial (16HBE) cells were used to assess ZCL's impact on acetylcholine (Ach) induced tracheal contraction, tumor necrosis factor α (TNF-α) induced bronchial inflammation, and transforming growth factor-β1 (TGF-β1) induced airway remodeling. Cell viability and gene expression were assessed using MTT assays, qPCR. RNA-seq (gene expression analysis) was employed to explore the novel mechanisms of ZCL in OVA-induced bronchial asthma.RESULTSIn this study, we found that ZCL reduces Ach-induced contraction of isolated guinea pig trachea, suppress TNF-α-induced interleukin (IL)-1β, IL-6, and IL-8 and TGF-β1-induced E-cadherin, α-SMA, Vimentin, N-cadherin mRNA expression in the 16HBE. Transcriptomic analysis of lung tissue from mice with OVA-induced bronchial asthma suggests that ZCL may alleviate asthma symptoms by modulating BPIFA1, HIF3Α, CTXN3, GRFA3, PPEF1, KSR2, and CDSN.CONCLUSIONZCL alleviates asthma by suppressing tracheal contractions, inflammation, and epithelial-to-mesenchymal transition. ZCL effect on asthma is likely through the upregulation of BPIFA1 expression thus providing the molecular insight for the treatment of asthma. The findings suggest that ZCL holds promise as a asthma therapeutic approach, and further research is needed to explore its full clinical potential. Future studies should focus on optimizing dosage, evaluating long-term efficacy, and investigating potential synergistic effects with existing treatments to enhance asthma management and patient outcomes.

2025-01-15·Journal of Pathology and Translational Medicine

PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in nasopharyngeal carcinoma

Article

作者: Liu, Qingluan ; Li, Xiayu ; Feng, Ranran ; Guo, Yilin ; Jiang, Su ; Shi, Lei ; Xiong, Wei ; Liu, Yijun ; Zhou, Jieyu ; Fan, Songqing ; Chen, Meilin ; Tian, Ziying ; Li, Guiyuan ; Zhang, Wenling

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear.Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP).Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin.Conclusions: PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

项与 BPIFA1 相关的新闻（医药）

2023-12-23

·今日头条

新思路！中南湘雅学者发现鼻咽癌最新免疫治疗策略

本文为转化医学网原创，转载请注明出处作者：Rainbow 导读：将巨噬细胞重编程为M1表型是诱导抗癌免疫的一种新策略。 12月21日，中南大学湘雅医院研究团队在期刊《Cell Death & Disease》上在线发表题为“USP7 inhibits the progression of nasopharyngeal carcinoma via promoting SPLUNC1-mediated M1 macrophage polarization through TRIM24”的研究论文，研究表明， USP7通过去泛素化和稳定TRIM24来重编程巨噬细胞为M1表型，从而增强SPLUNC1的表达，最终抑制了鼻咽癌的生长和转移。研究表明，针对USP7/TRIM24/SPLUNC1级联可能抑制免疫抑制作用，代表了一种有效的鼻咽癌免疫治疗策略。研究发现极大地贡献了对USP7在调控鼻咽癌进展机制和功能的理解。因此，研究结果为鼻咽癌的治疗提供了一种新颖的治疗思路，有望极大改善患者的预后。 https://www.nature.com/articles/s41419-023-06368-w 研究背景 01 鼻咽癌（NPC）是发生在鼻咽部的常见恶性肿瘤，占所有头颈肿瘤的约78％。目前，NPC的主要治疗方法是手术切除后联合放疗和化疗，然而，对于出现转移的NPC患者预后并不理想。因此，迫切需要阐明NPC细胞转移的机制并找到新的干预措施。巨噬细胞，在癌症中也被称为肿瘤相关巨噬细胞，通常表现为M2表型，并促进肿瘤的发展。而M1表型巨噬细胞则产生促炎症Th1免疫反应并具有杀伤肿瘤的活性。肿瘤相关巨噬细胞存在于NPC的肿瘤微环境中，并已报道与NPC患者的预后有关。然而，在NPC进展过程中，巨噬细胞极化的调节机制尚未得到阐明。短腭、肺和鼻上皮克隆1（SPLUNC1）是在鼻咽部表达的PLUNC家族成员，具有宿主防御性质。已经证明SPLUNC1能够保护免受革兰氏阴性细菌引起的呼吸道炎症。到目前为止，SPLUNC1是否能通过调节巨噬细胞极化来延缓NPC进展仍不清楚。泛素特异性加工酶7（USP7）是一个关键的去泛素化酶。已经有文献证实，USP7通过调节特定蛋白质的稳定性和功能，在肿瘤发展中发挥着重要作用。通过生物信息学分析，研究人员发现USP7具有去泛素化和稳定TRIM24的潜力。然而，USP7是否可以通过去泛素化和稳定TRIM24来影响NPC的进展，并随后调节SPLUNC1介导的M1型巨噬细胞极化，仍然不清楚。 SPLUNC1诱导的M1型巨噬细胞极化抑制了鼻咽癌细胞的生长和迁移 02 为了确定SPLUNC1介导的M1型巨噬细胞极化是否发挥了抗肿瘤作用，将鼻咽癌细胞（NPC/HK-1和CNE3）与THP-1源Mφs的培养基混合。与对照组相比，使用该培养基处理抑制了NPC细胞的生长，而在THP-1源Mφs中敲除SPLUNC1则破坏了这一结果。培养基的添加抑制了NPC细胞的迁移，而SPLUNC1沉默则对此产生了相反的效应。相反，使用SPLUNC1过表达的THP-1源Mφs的培养基进一步加强了THP-1源Mφs培养基对NPC细胞增殖和迁移的抑制作用。这些发现表明，在体外SPLUNC1诱导的M1型巨噬细胞极化抑制了NPC细胞的生长和转移。研究结果 03 综上所述，研究表明， USP7通过去泛素化和稳定TRIM24来重编程巨噬细胞为M1表型，从而增强SPLUNC1的表达，最终抑制了鼻咽癌的生长和转移。研究表明，针对USP7/TRIM24/SPLUNC1级联可能抑制免疫抑制作用，代表了一种有效的鼻咽癌免疫治疗策略。研究发现极大地贡献了对USP7在调控鼻咽癌进展机制和功能的理解。因此，研究结果为鼻咽癌的治疗提供了一种新颖的治疗思路，有望极大改善患者的预后。参考资料： https://www.nature.com/articles/s41419-023-06368-w 注：本文旨在介绍医学研究进展，不能作为治疗方案参考。如需获得健康指导，请至正规医院就诊。热门·直播/活动 🕓 北京｜12月19日-20日 ▶第四届单细胞测序技术应用研讨会暨单细胞&空间组学研讨会（日程稍后公布）点击对应文字查看详情

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