更新于：2024-11-01

BPIFA1

更新于：2024-11-01

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:23499554, PubMed:23132494). 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:23499554, PubMed:23132494, 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:24124190, PubMed:24043776). 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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277

项与 BPIFA1 相关的文献（医药）

2024-11-01·Cell Calcium

ELD607 specifically traffics Orai1 to the lysosome leading to inhibition of store operated calcium entry

Article

作者: Wrennall, Joe A ; Tarran, Robert ; Flori Sassano, M ; Goriounova, Alexandra S

Orai1 is a plasma membrane Ca²⁺ channel involved in store operated calcium entry (SOCE). SOCE can regulate cell growth, exocytosis, gene expression and inflammation. We previously found that short palate lung and nasal epithelial clone 1's (SPLUNC1) sixth α-helix (α6) bound Orai1 to inhibit SOCE. SPLUNC1 was not proteolytically stable, so we developed ELD607, an 11 amino acid peptide based on SPLUNC1's α6 region which was more stable and more potent than SPLUNC1/α6. Here, we studied ELD607's mechanism of action. We overexpressed either Orai1-HA or Orai1-YFP in HEK293T cells to probe ELD607-Orai1 interactions by confocal microscopy. We also measured changes in Fluo-4 fluorescence in a multiplate reader as a marker of cytoplasmic Ca²⁺ levels. ELD607 internalized Orai1 independently of STIM1. Both 15 min and 3 h exposure to ELD607 similarly depleted Orai1 in the plasma membrane. However, 3 h exposure to ELD607 yielded greater inhibition of SOCE. ELD607 continued to colocalize with Orai1 after internalization and this process was dependent on the presence of the ubiquitin ligase NEDD4.2. Similarly, ELD607 increased the colocalization between Orai1 and ubiquitin. ELD607 also increased the colocalization between Orai1 and Rab5 and 7, but not Rab11, suggesting that Orai1 trafficked through early and late but not recycling endosomes. Finally, ELD607 caused Orai1, but not Orai2, Orai3, or STIM1 to traffic to lysosomes. We conclude that ELD607 rapidly binds to Orai1 and works in an identical fashion as full length SPLUNC1 by internalizing Orai1 and sending it to lysosomes, leading to a decrease in SOCE.

2024-10-01·International Journal of Rheumatic Diseases

BPIFA1 alleviates allergic rhinitis by regulating the NF‐κB signaling pathway and Treg/Th17 balance

Article

作者: Yang, Ying ; Xu, Hongyan ; Li, Shidong

AbstractAimAllergic rhinitis (AR) is an allergic condition characterized by inflammation of the nasal mucosa. Bacterial permeability‐increasing family member A1 (BPIFA1) exhibits anti‐inflammatory properties; however, its impact on AR remains unclear. Aim of this study is to investigate the expression and function of BPIFA1 in AR and its influence on inflammation and immune regulation in a mouse model of AR induced by ovalbumin (OVA).MethodsThe expression of BPIFA1 was analyzed using quantitative real‐time PCR (qRT‐PCR) and immunohistochemistry (IHC). Morphological assessments of nasal mucosal tissues were conducted. Levels of inflammatory mediators in nasal lavage fluid (NALF) and serum were quantified using enzyme‐linked immunosorbent assay (ELISA) kits. Protein expressions of BPIFA1, phosphorylated and total p65 (p‐p65/p65), and IκBα were evaluated through Western blot analysis. The total cell counts, including epithelial cells, eosinophils, and lymphocytes in NALF, were determined using a hemocytometer. A mouse model of AR was established by OVA management.ResultsBPIFA1 expression was found to be reduced in the nasal mucosa tissues of patients with AR, suggesting a potential role in the disease's progression. We successfully developed a mouse model of AR, where BPIFA1 was similarly downregulated, indicating its possible involvement in modulating the NF‐κB signaling pathway. Overexpression of BPIFA1 in this model attenuated inflammation and allergic responses by inhibiting the NF‐κB pathway. Additionally, overexpression of BPIFA1 promoted the differentiation of regulatory T cells (Treg) and inhibited the differentiation of T helper 17 cells (Th17) in the NALF of AR mice, further demonstrating its regulatory impact on immune responses. The study confirmed that BPIFA1 upregulation reduced the levels of inflammatory cytokines TNF‐α and IL‐6, decreased infiltration of inflammatory cells, and modulated antigen‐specific immunoglobulin levels and histamine in serum.ConclusionBPIFA1 mitigated both inflammatory and allergic responses in AR mice induced by OVA through the modulation of the NF‐κB signaling pathway and the balance between regulatory T cells (Treg) and T helper 17 cells (Th17). These findings suggest that BPIFA1 could serve as a novel biomarker and therapeutic target for AR, offering potential for the development of targeted treatments to improve patient outcomes.

2024-05-13·Biomacromolecules

Correction to “Lung SPLUNC1 Peptide Derivatives in the Lipid Membrane Headgroup Kill Gram-Negative Planktonic and Biofilm Bacteria”

作者: Vijai, Aishwarya ; Gong, Yuqi ; Di, Yuan-Pu ; Qin, Weiheng ; Kang, Ann ; Mitra, Saheli ; Lin, Qiao ; Chen, Jespar ; Tristram-Nagle, Stephanie ; Jakkampudi, Tanvi ; Wang, Runxuan ; Ryan, Emma ; Heinrich, Frank ; Song, Junming

SPLUNC1 (short palate lung and nasal epithelial clone 1) is a multifunctional host defense protein found in human respiratory tract with antimicrobial properties.In this work, we compare the biol. activities of four SPLUNC1 antimicrobial peptide (AMP) derivatives using paired clin. isolates of the Gram-neg. (G(-)) bacteria Klebsiella pneumoniae, obtained from 11 patients with/without colistin resistance.Secondary structural studies were carried out to study interactions between the AMPs and lipid model membranes (LMMs) utilizing CD (CD).Two peptides were further characterized using X-ray diffuse scattering (XDS) and neutron reflectivity (NR).A4-153 displayed superior antibacterial activity in both G(-) planktonic cultures and biofilms.NR and XDS revealed that A4-153 (highest activity) is located primarily in membrane headgroups, while A4-198 (lowest activity) is located in hydrophobic interior.CD revealed that A4-153 is helical, while A4-198 has little helical character, demonstrating that helicity and efficacy are correlated in these SPLUNC1 AMPs.

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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