AbstractSepsis, a life-threatening condition caused by infection, is characterized by the dysregulation of immune responses and activation of monocytes. Plac8, a protein, has been implicated in various inflammatory conditions. This study aimed to investigate the effect of Plac8 upregulation on monocyte proliferation and activation in sepsis patients.

摘要脓毒症是由感染引起的危及生命的疾病，其特征是免疫反应失调和单核细胞活化。Plac8是一种蛋白质，与各种炎症有关。本研究旨在探讨Plac8上调对脓毒症患者单核细胞增殖和活化的影响。

Peripheral blood samples were collected from healthy individuals and sepsis patients. Monocytes were stimulated with lipopolysaccharide (LPS) to create an in vitro sepsis model, while a murine sepsis model was established using cecal ligation and puncture (CLP). The levels of monocyte markers, proliferation index (PI), and pro-inflammatory cytokines were assessed using flow cytometry and qPCR, respectively.

从健康个体和败血症患者收集外周血样本。用脂多糖（LPS）刺激单核细胞以产生体外败血症模型，同时使用盲肠结扎和穿刺（CLP）建立小鼠败血症模型。分别使用流式细胞术和qPCR评估单核细胞标志物，增殖指数（PI）和促炎细胞因子的水平。

Plac8 and phosphorylated ERK protein levels were determined by western blot, and TNF-α, IL-6, and IL-10 levels were quantified using ELISA. The CCK-8 assay was used to evaluate PBMC proliferation and activation. The results showed that Plac8 was highly expressed in sepsis models, promoting the survival, proliferation, and activation of monocytes.

通过蛋白质印迹测定Plac8和磷酸化的ERK蛋白水平，并使用ELISA定量TNF-α，IL-6和IL-10水平。CCK-8测定用于评估PBMC增殖和活化。结果表明，Plac8在脓毒症模型中高表达，促进单核细胞的存活，增殖和活化。

Plac8 upregulation activated the ERK pathway, leading to increased phosphorylation of ERK protein and elevated levels of CD14, CD16, TNF-α, IL-6, Plac8, and IL-10. In sepsis mice, Plac8 overexpression similarly activated the ERK pathway and promoted the survival, proliferation, and activation of monocytes.

Plac8上调激活ERK途径，导致ERK蛋白磷酸化增加，CD14，CD16，TNF-α，IL-6，Plac8和IL-10水平升高。在败血症小鼠中，Plac8过表达类似地激活了ERK途径并促进了单核细胞的存活，增殖和活化。

In conclusion, the upregulation of Plac8 enhances the activation of the ERK pathway and promotes monocyte proliferation and activation in sepsis patients..

总之，Plac8的上调增强了ERK途径的激活，并促进了脓毒症患者的单核细胞增殖和活化。。

IntroductionSepsis is a life-threatening disease caused by an uncontrolled host response to infection, and it remains a major cause of death and severe illness worldwide, imposing a significant burden on global healthcare systems [1,2,3]. Despite advances in antimicrobial therapy and intensive care techniques, the incidence of sepsis continues to rise, attributed to the aging population and the increasing prevalence of antibiotic-resistant pathogens [2, 4, 5].

引言脓毒症是一种威胁生命的疾病，由宿主对感染的不受控制的反应引起，它仍然是全球死亡和严重疾病的主要原因，给全球医疗保健系统带来了沉重负担[1,2,3]。尽管抗菌治疗和重症监护技术取得了进展，但由于人口老龄化和抗生素耐药病原体的流行率不断增加，脓毒症的发病率继续上升[2，4，5]。

The complexity of sepsis arises from its heterogeneity, with diverse clinical manifestations ranging from systemic inflammatory response to severe septic shock and multiple organ dysfunction syndrome [6, 7]. Dysregulation of immune responses plays a central role in the pathophysiology of sepsis, and peripheral blood mononuclear cells (PBMCs) play a key role in this process [8,9,10].

脓毒症的复杂性源于其异质性，临床表现多样，从全身炎症反应到严重感染性休克和多器官功能障碍综合征[6，7]。免疫反应失调在脓毒症的病理生理学中起着核心作用，外周血单核细胞（PBMC）在这一过程中起着关键作用[8，9，10]。

Cells, including monocytes, lymphocytes, and dendritic cells, play important roles in balancing pro-inflammatory and anti-inflammatory responses [11, 12]. However, due to a limited understanding of the regulatory mechanisms governing PBMC function during the acute and recovery phases of sepsis, the clinical management of sepsis has become complex, highlighting the need for innovative research in this field.Monocytes, a crucial subset of PBMCs, play a dual role in sepsis by directing innate immune responses through pathogen recognition, cytokine production, and initiation of adaptive immunity.

细胞，包括单核细胞，淋巴细胞和树突状细胞，在平衡促炎和抗炎反应中发挥重要作用[11，12]。然而，由于对脓毒症急性期和恢复期PBMC功能调控机制的了解有限，脓毒症的临床管理变得复杂，突出了该领域创新研究的必要性。。

These cells exhibit significant plasticity, differentiating into various effector cells, including macrophages and dendritic cells, to adapt to the ever-changing septic environment [13,14,15]. The functional state of monocytes is a key factor determining the progression and outcomes of sepsis [16]. A deeper understanding of the biology of monocyte.

。单核细胞的功能状态是决定败血症进展和结局的关键因素〔16〕。对单核细胞生物学的更深入理解。

Data availability

数据可用性

The data that support the findings of this study are available on request from the corresponding author.

支持本研究结果的数据可应通讯作者的要求提供。

ReferencesRudd KE, Johnson SC, Agesa KM, Shackelford KA, Tsoi D, Kievlan DR, et al. Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study. Lancet. 2020;395:200–11. https://doi.org/10.1016/S0140-6736(19)32989-7.Article

参考文献Rudd KE，Johnson SC，Agesa KM，Shackelford KA，Tsoi D，Kievlan DR等。1990-2017年全球，地区和国家败血症发病率和死亡率：全球疾病负担研究分析。柳叶刀。2020年；395:200-11。https://doi.org/10.1016/S0140-6736（19） 32989-7.文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Liu D, Huang SY, Sun JH, Zhang HC, Cai QL, Gao C, et al. Sepsis-induced immunosuppression: mechanisms, diagnosis and current treatment options. Mil Med Res. 2022;9:56. https://doi.org/10.1186/s40779-022-00422-y.Article

刘德，黄世元，孙建华，张慧聪，蔡秋林，高超，等。脓毒症诱导的免疫抑制：机制，诊断和当前治疗选择。Mil Med Res.2022；9： 56页。https://doi.org/10.1186/s40779-022-00422-y.Article

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

van der Poll T, Shankar-Hari M, Wiersinga WJ. The immunology of sepsis. Immunity. 2021;54:2450–64. https://doi.org/10.1016/j.immuni.2021.10.012.Article

范德波尔T，Shankar Hari M，维尔辛加WJ。脓毒症的免疫学。豁免。2021年；54:2450-64。https://doi.org/10.1016/j.immuni.2021.10.012.Article

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Purcarea A, Sovaila S. Sepsis, a 2020 review for the internist. Rom J Intern Med. 2020;58:129–37. https://doi.org/10.2478/rjim-2020-0012.Article

Purcarea A，Sovaila S.败血症，2020年内科医生评论。Rom J Intern Med。2020；58:129-37。https://doi.org/10.2478/rjim-2020-0012.Article

PubMed

PubMed

Google Scholar

谷歌学者

Gavelli F, Castello LM, Avanzi GC. Management of sepsis and septic shock in the emergency department. Intern Emerg Med. 2021;16:1649–61. https://doi.org/10.1007/s11739-021-02735-7.Article

加维利F，卡斯特罗LM，阿万齐GC。急诊科脓毒症和感染性休克的管理。实习医生Emerg Med。2021；16： 1649-61年。https://doi.org/10.1007/s11739-021-02735-7.Article

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Leise BS, Fugler LA. Laminitis updates: sepsis/systemic inflammatory response syndrome-associated laminitis. Vet Clin Equine Pract. 2021;37:639–56. https://doi.org/10.1016/j.cveq.2021.08.003.Article

Leise BS，Fugler LA。椎板炎更新：败血症/全身炎症反应综合征相关的椎板炎。兽医临床马实践。2021年；。https://doi.org/10.1016/j.cveq.2021.08.003.Article

Google Scholar

谷歌学者

Meyr AJ, Dougherty M, Kwaadu KY. An evaluation of patient characteristics associated with medical disposition in the surgical treatment of ankle fractures. J Foot Ankle Surg. 2022;61:72–78. https://doi.org/10.1053/j.jfas.2021.06.009.Article

。J足踝外科杂志2022；61:72-78。https://doi.org/10.1053/j.jfas.2021.06.009.Article

PubMed

PubMed

Google Scholar

谷歌学者

Wang T, Zhang X, Liu Z, Yao T, Zheng D, Gan J, et al. Single-cell RNA sequencing reveals the sustained immune cell dysfunction in the pathogenesis of sepsis secondary to bacterial pneumonia. Genomics. 2021;113:1219–33. https://doi.org/10.1016/j.ygeno.2021.01.026.Article

Wang T，Zhang X，Liu Z，Yao T，Zheng D，Gan J，et al。单细胞RNA测序揭示了细菌性肺炎继发脓毒症发病机制中持续的免疫细胞功能障碍。基因组学。2021年；113:1219-33。https://doi.org/10.1016/j.ygeno.2021.01.026.Article

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Pickering H, Sen S, Arakawa-Hoyt J, Ishiyama K, Sun Y, Parmar R, et al. NK and CD8+ T cell phenotypes predict onset and control of CMV viremia after kidney transplant. JCI Insight. 2021;6:e153175. https://doi.org/10.1172/jci.insight.153175.Article

Pickering H，Sen S，Arakawa-Hoyt J，Ishiyama K，Sun Y，Parmar R等。NK和CD8+T细胞表型预测肾移植后CMV病毒血症的发生和控制。JCI Insight。2021年；6： e153175。https://doi.org/10.1172/jci.insight.153175.Article

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Wu T, Liang X, Jiang Y, Chen Q, Zhang H, Zhang S, et al. Comprehensive transcriptome profiling of peripheral blood mononuclear cells from patients with sepsis. Int J Med Sci. 2020;17:2077–86. https://doi.org/10.7150/ijms.46910.Article

Wu T，Liang X，Jiang Y，Chen Q，Zhang H，Zhang S，等。脓毒症患者外周血单核细胞的综合转录组分析。国际医学科学杂志。2020年；17： 2077-86年。https://doi.org/10.7150/ijms.46910.Article

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Schenz J, Tamulyte S, Nusshag C, Brenner T, Poschet G, Weigand MA, et al. Population-specific metabolic alterations in professional antigen-presenting cells contribute to sepsis-associated immunosuppression. Shock. 2020;53:5–15. https://doi.org/10.1097/SHK.0000000000001337.Article

Schenz J，Tamulyte S，Nusshag C，Brenner T，Poschet G，Weigand MA等。专业抗原呈递细胞中的群体特异性代谢改变有助于败血症相关的免疫抑制。震惊。2020年；53:5-15。https://doi.org/10.1097/SHK.0000000000001337.Article

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Washburn ML, Wang Z, Walton AH, Goedegebuure SP, Figueroa DJ, Van Horn S, et al. T cell- and monocyte-specific RNA-sequencing analysis in septic and nonseptic critically Ill patients and in patients with cancer. J Immunol. 2019;203:1897–908. https://doi.org/10.4049/jimmunol.1900560.Article .

Washburn ML，Wang Z，Walton AH，Goedegebuure SP，Figueroa DJ，Van Horn S等。脓毒症和非脓毒症重症患者以及癌症患者的T细胞和单核细胞特异性RNA测序分析。免疫杂志。2019年；203:1897年至908年。https://doi.org/10.4049/jimmunol.1900560.Article。

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Chang JG, Tu SJ, Huang CM, Chen YC, Chiang HS, Lee YT, et al. Single-cell RNA sequencing of immune cells in patients with acute gout. Sci Rep. 2022;12:22130. https://doi.org/10.1038/s41598-022-25871-2.Article

Chang JG，Tu SJ，Huang CM，Chen YC，Chiang HS，Lee YT，等。急性痛风患者免疫细胞的单细胞RNA测序。Sci代表2022；12： 22130页。https://doi.org/10.1038/s41598-022-25871-2.Article

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Crawford LB, Diggins NL, Caposio P, Hancock MH. Advances in model systems for human cytomegalovirus latency and reactivation. mBio. 2022;13:e0172421. https://doi.org/10.1128/mbio.01724-21.Article

Crawford LB，Diggins NL，Caposio P，Hancock MH。人类巨细胞病毒潜伏期和再激活模型系统的进展。mBio公司。2022年；13： e0172421。https://doi.org/10.1128/mbio.01724-21.Article

PubMed

PubMed

Google Scholar

谷歌学者

Hettema JM, van den Oord EJCG, Zhao M, et al. Methylome-wide association study of anxiety disorders. Mol Psychiatry. 2023;28:3484–92. https://doi.org/10.1038/s41380-023-02205-w.Li LL, Dai B, Sun YH, Zhang TT. Monocytes undergo functional reprogramming to generate immunosuppression through HIF-1α signaling pathway in the late phase of sepsis.

Hettema JM，van den Oord EJCG，Zhao M，等。焦虑症的甲基化全关联研究。摩尔精神病学。；28:3484-92。https://doi.org/10.1038/s41380-023-02205-w.LiLL，Dai B，Sun YH，Zhang TT。单核细胞在脓毒症晚期通过HIF-1α信号通路进行功能重编程以产生免疫抑制。

Mediators Inflamm. 2020;2020:4235909. https://doi.org/10.1155/2020/4235909.Article .

Mediators Inflamm. 2020;2020:4235909. https://doi.org/10.1155/2020/4235909.Article .

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Trzeciak A, Lerman YV, Kim TH, Kim MR, Mai N, Halterman MW, et al. Long-term microgliosis driven by acute systemic inflammation. J Immunol. 2019;203:2979–89. https://doi.org/10.4049/jimmunol.1900317.Article

Trzeciak A，Lerman YV，Kim TH，Kim MR，Mai N，Halterman MW等。由急性全身炎症驱动的长期小胶质细胞增生。免疫杂志。2019年；。https://doi.org/10.4049/jimmunol.1900317.Article

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Avendaño-Ortiz J, Redondo-Calvo FJ, Lozano-Rodríguez R, Terrón-Arcos V, Bergón-Gutiérrez M, Rodríguez-Jiménez C, et al. Thiosulfinate-enriched Allium sativum extract exhibits differential effects between healthy and sepsis patients: the implication of HIF-1α. Int J Mol Sci. 2023;24:6234.

Avendaño-Ortiz J，Redondo Calvo FJ，Lozano Rodríguez R，Terrón-Arcos V，Bergón-Gutiérrez M，Rodríguez Jiménez C等。富含硫代硫酸盐的大蒜提取物在健康和败血症患者之间表现出不同的作用：HIF-1α的含义。国际分子科学杂志。；24:6234。

https://doi.org/10.3390/ijms24076234.Article .

https://doi.org/10.3390/ijms24076234.Article .

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

He F, Wu X, Zhang Q, Li Y, Ye Y, Li P, et al. Bacteriostatic potential of melatonin: therapeutic standing and mechanistic insights. Front Immunol. 2021;12:683879. https://doi.org/10.3389/fimmu.2021.683879.Article

何福，吴X，张Q，李Y，叶Y，李P，等。褪黑激素的抑菌潜力：治疗立场和机制见解。前免疫。2021年；12： 683879页。https://doi.org/10.3389/fimmu.2021.683879.Article

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Lee H, Kim JI, Park JS, Roh JI, Lee J, Kang BC, et al. CRISPR/Cas9-mediated generation of a Plac8 knockout mouse model. Lab Anim Res. 2018;34:279–87. https://doi.org/10.5625/lar.2018.34.4.279.Article

Lee H，Kim JI，Park JS，Roh JI，Lee J，Kang BC等。CRISPR/Cas9介导的Plac8基因敲除小鼠模型的产生。Lab Anim Res.2018；34:279-87。https://doi.org/10.5625/lar.2018.34.4.279.Article

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Pang J, Li H, Zhang X, Luo Z, Chen Y, Zhao H, et al. Application of novel transcription factor machine learning model and targeted drug combination therapy strategy in triple negative breast cancer. Int J Mol Sci. 2023;24:13497. https://doi.org/10.3390/ijms241713497.Article

庞J，李H，张X，罗Z，陈Y，赵H，等。新型转录因子机器学习模型和靶向药物联合治疗策略在三阴性乳腺癌中的应用。国际分子科学杂志。；24:13497。https://doi.org/10.3390/ijms241713497.Article

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Mao M, Chen Y, Yang J, Cheng Y, Xu L, Ji F, et al. Modification of PLAC8 by UFM1 affects tumorous proliferation and immune response by impacting PD-L1 levels in triple-negative breast cancer. J Immunother Cancer. 2022;10:e005668. https://doi.org/10.1136/jitc-2022-005668.Article

Mao M，Chen Y，Yang J，Cheng Y，Xu L，Ji F等。UFM1对PLAC8的修饰通过影响三阴性乳腺癌中的PD-L1水平来影响肿瘤增殖和免疫应答。J免疫治疗癌症。2022年；10： e005668。https://doi.org/10.1136/jitc-2022-005668.Article

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Kemp SB, Steele NG, Carpenter ES, Donahue KL, Bushnell GG, Morris AH, et al. Pancreatic cancer is marked by complement-high blood monocytes and tumor-associated macrophages. Life Sci Alliance. 2021;4:e202000935. https://doi.org/10.26508/lsa.202000935.Article

Kemp SB，Steele NG，Carpenter ES，Donahue KL，Bushnell GG，Morris AH等。胰腺癌的特征是补体高血单核细胞和肿瘤相关巨噬细胞。生命科学联盟。2021年；4： e202000935。https://doi.org/10.26508/lsa.202000935.Article

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Gravrand V, Mellot F, Ackermann F, Ballester MC, Zuber B, Kirk JT, et al. Stratification of COVID-19 severity using SeptiCyte RAPID, a novel host immune response test. Viruses. 2023;15:419. https://doi.org/10.3390/v15020419.Article

Gravrand V，Mellot F，Ackermann F，Ballester MC，Zuber B，Kirk JT等。使用新型宿主免疫应答测试脓毒症快速对COVID-19严重程度进行分层。病毒。；15： 。https://doi.org/10.3390/v15020419.Article

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Tsuboi H, Segawa S, Yagishita M, Toko H, Honda F, Kitada A, et al. Activation mechanisms of monocytes/macrophages in adult-onset still disease. Front Immunol. 2022;13:953730. https://doi.org/10.3389/fimmu.2022.953730.Article

Tsuboi H，Segawa S，Yagishita M，Toko H，Honda F，Kitada A等。成人still病中单核细胞/巨噬细胞的激活机制。前免疫。2022年；13： 953730页。https://doi.org/10.3389/fimmu.2022.953730.Article

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Yang Q, Ni L, Imani S, Xiang Z, Hai R, Ding R, et al. Anlotinib suppresses colorectal cancer proliferation and angiogenesis via inhibition of AKT/ERK signaling cascade. Cancer Manag Res. 2020;12:4937–48. https://doi.org/10.2147/CMAR.S252181.Article

Yang Q，Ni L，Imani S，Xiang Z，Hai R，Ding R等。阿洛替尼通过抑制AKT/ERK信号级联抑制结直肠癌增殖和血管生成。癌症管理Res.2020；12： 4937-48页。https://doi.org/10.2147/CMAR.S252181.Article

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Javaid S, Schaefer A, Goodwin CM, Nguyen VV, Massey FL, Pierobon M, et al. Concurrent inhibition of ERK and farnesyltransferase suppresses the growth of HRAS mutant head and neck squamous cell carcinoma. Mol Cancer Ther. 2022;21:762–74. https://doi.org/10.1158/1535-7163.MCT-21-0142.Article .

Javaid S，Schaefer A，Goodwin CM，Nguyen VV，Massey FL，Pierobon M等。同时抑制ERK和法尼基转移酶抑制HRAS突变头颈部鳞状细胞癌的生长。摩尔癌症治疗。2022年；21:762-74。https://doi.org/10.1158/1535-7163.MCT-21-0142.Article。

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Ren M, Zhao Y, He Z, Lin J, Xu C, Liu F, et al. Baicalein inhibits inflammatory response and promotes osteogenic activity in periodontal ligament cells challenged with lipopolysaccharides. BMC Complement Med Ther. 2021;21:43. https://doi.org/10.1186/s12906-021-03213-5.Article

任M，赵Y，何Z，林J，徐C，刘F，等。黄芩素抑制脂多糖攻击的牙周膜细胞的炎症反应并促进成骨活性。BMC补充医学。2021年；21:43。https://doi.org/10.1186/s12906-021-03213-5.Article

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Zhao C, Zou T, Tang R, Zhu C. Placenta-specific 8 (PLAC8) mediates inflammation and mobility of the hPDLCs via MEK/ERK signaling pathway. Int Immunopharmacol. 2022;103:108459. https://doi.org/10.1016/j.intimp.2021.108459.Article

Zhao C，Zou T，Tang R，Zhu C.胎盘特异性8（PLAC8）通过MEK/ERK信号通路介导hPDLCs的炎症和迁移。国际免疫药理学。2022年；103:108459。https://doi.org/10.1016/j.intimp.2021.108459.Article

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Mao M, Hu D, Yang J, Chen Y, Zhang X, Shen J, et al. Regulation of tamoxifen sensitivity by the PLAC8/MAPK pathway axis is antagonized by curcumin-induced protein stability change. J Mol Med. 2021;99:845–58. https://doi.org/10.1007/s00109-021-02047-5.Article

Mao M，Hu D，Yang J，Chen Y，Zhang X，Shen J，et al。姜黄素诱导的蛋白质稳定性变化拮抗了PLAC8/MAPK途径轴对他莫昔芬敏感性的调节。J Mol Med。2021；99:845-58。https://doi.org/10.1007/s00109-021-02047-5.Article

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Zeng X, Liu Q, Yang Y, Jia W, Li S, He D, et al. Placenta-specific protein 8 promotes the proliferation of lung adenocarcinoma PC-9 cells and their tolerance to an epidermal growth factor receptor tyrosine kinase inhibitor by activating the ERK signaling pathway. Oncol Lett. 2019;18:5621–7.

Zeng X，Liu Q，Yang Y，Jia W，Li S，He D，et al。胎盘特异性蛋白8通过激活ERK信号通路促进肺腺癌PC-9细胞的增殖及其对表皮生长因子受体酪氨酸激酶抑制剂的耐受性。Oncol Lett。2019年；18： 5621–7。

https://doi.org/10.3892/ol.2019.10911.Article .

https://doi.org/10.3892/ol.2019.10911.Article.

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Li R, Li M, Chen L. [Knockdown of placental-specific protein 8 (PLAC8) inhibits proliferation and promotes apoptosis of human embryonic stem cells]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2020;36:1089–94.An H, Liu Y, Fang L, Shu M, Zhai Q, Chen J. Placenta-specific 8 facilitates the infection of duck hepatitis A virus type 1 by inhibiting the TLR7 MyD88-dependent signaling pathway.

Li R，Li M，Chen L.[胎盘特异性蛋白8（PLAC8）的敲低抑制人胚胎干细胞的增殖并促进其凋亡]。《西宝玉粉子面医学杂志》。2020年；36:1089–94.An H，Liu Y，Fang L，Shu M，Zhai Q，Chen J.胎盘特异性8通过抑制TLR7 MyD88依赖性信号通路促进鸭甲型肝炎病毒1型的感染。

Poult Sci. 2023;102:102724. https://doi.org/10.1016/j.psj.2023.102724.Article .

Poult Sci. 2023;102:102724. https://doi.org/10.1016/j.psj.2023.102724.Article .

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Yang L, Zhou R, Tong Y, Chen P, Shen Y, Miao S, et al. Neuroprotection by dihydrotestosterone in LPS-induced neuroinflammation. Neurobiol Dis. 2020;140:104814. https://doi.org/10.1016/j.nbd.2020.104814.Article

杨丽，周若，童毅，陈平，沈毅，缪S，等。二氢睾酮对LPS诱导的神经炎症的神经保护作用。神经生物学疾病。2020年；140:104814。https://doi.org/10.1016/j.nbd.2020.104814.Article

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Tan H, Chen J, Li Y, Li Y, Zhong Y, Li G, et al. Glabridin, a bioactive component of licorice, ameliorates diabetic nephropathy by regulating ferroptosis and the VEGF/Akt/ERK pathways. Mol Med. 2022;28:58. https://doi.org/10.1186/s10020-022-00481-w.Article

Tan H，Chen J，Li Y，Li Y，Zhong Y，Li G等。甘草的生物活性成分Glabridin通过调节铁蛋白沉积和VEGF/Akt/ERK途径来改善糖尿病肾病。摩尔医学2022；28:58。https://doi.org/10.1186/s10020-022-00481-w.Article

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

de Los Reyes Corrales T, Losada-Pérez M, Casas-Tintó S. JNK Pathway in CNS Pathologies. Int J Mol Sci. 2021;22:3883. https://doi.org/10.3390/ijms22083883.Article

来自Corrales T国王，Losada-Perez M，Casas-Tintos。CNS病理学中的JNK途径。国际分子科学杂志。2021年；22:3883。https://doi.org/10.3390/ijms22083883.Article

CAS

中科院

Google Scholar

谷歌学者

Tang L, Wu M, Lu S, Zhang H, Shen Y, Shen C, et al. Fgf9 negatively regulates bone mass by inhibiting osteogenesis and promoting osteoclastogenesis via MAPK and PI3K/AKT signaling. J Bone Miner Res. 2021;36:779–91. https://doi.org/10.1002/jbmr.4230.Article

Tang L，Wu M，Lu S，Zhang H，Shen Y，Shen C等。Fgf9通过MAPK和PI3K/AKT信号传导抑制成骨和促进破骨细胞生成来负调节骨量。J Bone Miner Res.2021；36:779-91。https://doi.org/10.1002/jbmr.4230.Article

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Wu X, Wang A, Zhang S, Wang X, Guo D, Zhu W, et al. Multiomic landscape of immune pathogenesis in Kimura’s disease. iScience. 2023;26:106559. https://doi.org/10.1016/j.isci.2023.106559.Article

Wu X，Wang A，Zhang S，Wang X，Guo D，Zhu W，等。木村病免疫发病机制的多组学景观。iScience。；26:106559。https://doi.org/10.1016/j.isci.2023.106559.Article

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Ugalde AP, Bretones G, Rodríguez D, Quesada V, Llorente F, Fernández-Delgado R, et al. Autophagy-linked plasma and lysosomal membrane protein PLAC8 is a key host factor for SARS-CoV-2 entry into human cells. EMBO J. 2022;41:e110727. https://doi.org/10.15252/embj.2022110727.Article

Ugalde AP，Bretones G，Rodríguez D，Quesada V，Llorente F，Fernández-Delgado R等。自噬相关的血浆和溶酶体膜蛋白PLAC8是SARS-CoV-2进入人类细胞的关键宿主因子。EMBO J.2022；41:e110727。https://doi.org/10.15252/embj.2022110727.Article

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Almubarak A, Tanagala KKK, Papapanou PN, Lalla E, Momen-Heravi F. Disruption of monocyte and macrophage homeostasis in periodontitis. Front Immunol. 2020;11:330. https://doi.org/10.3389/fimmu.2020.00330.Article

Almubarak A，Tanagala KKK，Papapanou PN，Lalla E，Momen Heravi F.牙周炎中单核细胞和巨噬细胞稳态的破坏。前免疫。2020年；11： 330页。https://doi.org/10.3389/fimmu.2020.00330.Article

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Ye C, Zhu J, Wang J, Chen D, Meng L, Zhan Y, et al. Single-cell and spatial transcriptomics reveal the fibrosis-related immune landscape of biliary atresia. Clin Transl Med. 2022;12:e1070. https://doi.org/10.1002/ctm2.1070.Article

叶C，朱J，王J，陈D，孟L，詹Y，等。单细胞和空间转录组学揭示了胆道闭锁纤维化相关的免疫景观。临床翻译医学2022；12： e1070。https://doi.org/10.1002/ctm2.1070.Article

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Chi M, Tian Z, Ma K, Li Y, Wang L, Nasser MI, et al. The diseased kidney: aging and senescent immunology. Immun Ageing. 2022;19:58. https://doi.org/10.1186/s12979-022-00313-9.Article

Chi M，Tian Z，Ma K，Li Y，Wang L，Nasser MI，等。患病肾脏：衰老和衰老免疫学。免疫老化。2022年；19： 58页。https://doi.org/10.1186/s12979-022-00313-9.Article

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Hadjadj J, Yatim N, Barnabei L, Corneau A, Boussier J, Smith N, et al. Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Science. 2020;369:718–24. https://doi.org/10.1126/science.abc6027.Article

Hadjadj J，Yatim N，Barnabei L，Corneau A，Boussier J，Smith N等。严重COVID-19患者的I型干扰素活性和炎症反应受损。科学。2020年；369:718-24。https://doi.org/10.1126/science.abc6027.Article

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Wang XL, Chen F, Shi H, Zhang M, Yan L, Pei XY, et al. Oxymatrine inhibits neuroinflammation byRegulating M1/M2 polarization in N9 microglia through the TLR4/NF-κB pathway. Int Immunopharmacol. 2021;100:108139. https://doi.org/10.1016/j.intimp.2021.108139.Article

Wang XL，Chen F，Shi H，Zhang M，Yan L，Pei XY等。氧化苦参碱通过TLR4/NF-κB途径调节N9小胶质细胞中的M1/M2极化来抑制神经炎症。国际免疫药理学。2021年；100:108139。https://doi.org/10.1016/j.intimp.2021.108139.Article

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Zheng L, Tang X, Lu M, Sun S, Xie S, Cai J, et al. microRNA-421-3p prevents inflammatory response in cerebral ischemia/reperfusion injury through targeting m6A Reader YTHDF1 to inhibit p65 mRNA translation. Int Immunopharmacol. 2020;88:106937. https://doi.org/10.1016/j.intimp.2020.106937.Article .

。国际免疫药理学。2020年；88:106937。https://doi.org/10.1016/j.intimp.2020.106937.Article。

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Long Y, Wang L, Li Z. SP1-induced SNHG14 aggravates hypertrophic response in in vitro model of cardiac hypertrophy via up-regulation of PCDH17. J Cell Mol Med. 2020;24:7115–26. https://doi.org/10.1111/jcmm.15073.Article

Long Y，Wang L，Li Z.SP1诱导的SNHG14通过上调PCDH17在体外心脏肥大模型中加重肥大反应。J Cell Mol Med。2020；24:7115-26。https://doi.org/10.1111/jcmm.15073.Article

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Persich P, Engels GE, van Oeveren W, Galia E, Benay S, Thun S. Development of an in vitro system and model-based translational framework to assess haemolysis risk following intravenous abuse of medications containing polyethylene oxide. Toxicol Vitro. 2020;65:104776. https://doi.org/10.1016/j.tiv.2020.104776.Article .

Persich P，Engels GE，van Oeveren W，Galia E，Benay S，Thun S.开发体外系统和基于模型的翻译框架，以评估静脉内滥用含有聚环氧乙烷的药物后的溶血风险。毒理学体外。2020年；65:104776。https://doi.org/10.1016/j.tiv.2020.104776.Article。

CAS

中科院

Google Scholar

谷歌学者

Tasnim F, Huang X, Lee CZW, Ginhoux F, Yu H. Recent advances in models of immune-mediated drug-induced liver injury. Front Toxicol. 2021;3:605392. https://doi.org/10.3389/ftox.2021.605392.Article

Tasnim F，Huang X，Lee CZW，Ginhoux F，Yu H.免疫介导的药物性肝损伤模型的最新进展。前毒物。2021年；3： 605392页。https://doi.org/10.3389/ftox.2021.605392.Article

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Du K, Li S, Li C, Li P, Miao C, Luo T, et al. Modeling nonalcoholic fatty liver disease on a liver lobule chip with dual blood supply. Acta Biomater. 2021;134:228–39. https://doi.org/10.1016/j.actbio.2021.07.013.Article

Du K，Li S，Li C，Li P，Miao C，Luo T等。在具有双重血液供应的肝小叶芯片上模拟非酒精性脂肪肝疾病。生物计量学报。2021年；134:228-39。https://doi.org/10.1016/j.actbio.2021.07.013.Article

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Huang ML, Zou Y, Yang R, Jiang Y, Sheng JF, Han JB, et al. Placenta specific 8 gene induces epithelial-mesenchymal transition of nasopharyngeal carcinoma cells via the TGF-β/Smad pathway. Exp Cell Res. 2019;374:172–80. https://doi.org/10.1016/j.yexcr.2018.11.021.Article

Huang ML，Zou Y，Yang R，Jiang Y，Sheng JF，Han JB，et al。胎盘特异性8基因通过TGF-β/Smad途径诱导鼻咽癌细胞的上皮-间质转化。Exp Cell Res.2019；374:172-80。https://doi.org/10.1016/j.yexcr.2018.11.021.Article

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Sranujit RP, Noysang C, Tippayawat P, Kooltheat N, Luetragoon T, Usuwanthim K. Phytochemicals and immunomodulatory effect of Nelumbo nucifera flower extracts on human macrophages. Plants. 2021;10:2007. https://doi.org/10.3390/plants10102007.Article

Sranujit RP，Noysang C，Tippayawat P，Kooltheat N，Luetragoon T，Usuwanthim K.莲藕花提取物对人巨噬细胞的植物化学物质和免疫调节作用。植物。2021年；10： 2007年。https://doi.org/10.3390/plants10102007.Article

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Song R, He S, Wu Y, Chen W, Song J, Zhu Y, et al. Validation of reference genes for the normalization of the RT-qPCR in peripheral blood mononuclear cells of septic patients. Heliyon. 2023;9:e15269. https://doi.org/10.1016/j.heliyon.2023.e15269.Article

Song R，He S，Wu Y，Chen W，Song J，Zhu Y，et al。验证脓毒症患者外周血单核细胞中RT-qPCR正常化的参考基因。海伦。；9： e15269。https://doi.org/10.1016/j.heliyon.2023.e15269.Article

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Download referencesFundingThis work was supported by Tianjin Municipal Health Commission (RC20145 to TZ).Author informationAuthors and AffiliationsDepartment of General Surgery, Tianjin Medical University General Hospital, Tianjin, 300000, ChinaTeng ZhangDepartment of Minimally Invasive Surgery, Characteristics Medical Center of Chinese People Armed Police Force, Tianjin, ChinaJing-nan FuDepartment of General Surgery, Clinical Medical College and The First Affiliated Hospital of Chengdu Medical College, Chengdu, ChinaGui-bing ChenDepartment of Emergency, Beijing Tsinghua Changgung Hospital, Beijing, 102218, ChinaXiu ZhangAuthorsTeng ZhangView author publicationsYou can also search for this author in.

下载参考文献资助这项工作得到了天津市卫生委员会（RC20145 to TZ）的支持。作者信息作者及所属机构天津医科大学总医院普外科，天津，300000，张国栋，中国人民武装警察部队特色医学中心微创外科，天津，中国京南府普外科，临床医学院和成都医学院第一附属医院，成都，陈桂兵北京清华长庚医院急诊科，北京，102218，张国秀作者张国栋观点作者出版物您也可以在中搜索作者。

PubMed Google ScholarJing-nan FuView author publicationsYou can also search for this author in

PubMed Google ScholarJing nan FuView作者出版物您也可以在

PubMed Google ScholarGui-bing ChenView author publicationsYou can also search for this author in

PubMed Google ScholarGui bing ChenView作者出版物您也可以在

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PubMed Google ScholarContributionsTeng Zhang contributed to conceptualization, data curation, methodology, formal analysis, and the initial drafting of the manuscript. Jing-nan Fu and Xiu Zhang participated in data curation, investigation, visualization, and contributed to reviewing and editing the manuscript.

PubMed谷歌学术贡献Steng Zhang为概念化，数据管理，方法论，形式分析和手稿的初步起草做出了贡献。傅京南和张秀参与了数据管理，调查，可视化，并为稿件的审阅和编辑做出了贡献。

Gui-bing Chen provided supervision, managed project administration, secured funding, and contributed to reviewing and editing the manuscript. All authors actively contributed to the study’s design and execution, provided critical feedback during manuscript preparation, and gave their final approval for publication.Corresponding authorCorrespondence to.

陈桂冰提供监督，管理项目管理，获得资金，并为稿件的审查和编辑做出了贡献。所有作者都积极参与了研究的设计和执行，在稿件准备过程中提供了重要的反馈，并最终批准了发表。对应作者对应。

Teng Zhang.Ethics declarations

张腾。道德宣言

Competing interests

相互竞争的利益

The author declare no competing interests.

作者声明没有利益冲突。

Ethical approval

道德认可

All procedures involving the use of animals in research were authorized by the ethics committee of Tianjin Medical University General Hospital (approval no. IRB2022-DWFL-44).

所有涉及在研究中使用动物的程序均经天津医科大学总医院伦理委员会授权（批准号IRB2022-DWFL-44）。

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Reprints and permissionsAbout this articleCite this articleZhang, T., Fu, Jn., Chen, Gb. et al. Plac8-ERK pathway modulation of monocyte function in sepsis.

转载和许可本文引用本文Zhang，T.，Fu，Jn。，陈，英国。Plac8-ERK通路调节脓毒症单核细胞功能。

Cell Death Discov. 10, 308 (2024). https://doi.org/10.1038/s41420-024-02012-4Download citationReceived: 28 November 2023Revised: 03 May 2024Accepted: 07 May 2024Published: 03 July 2024DOI: https://doi.org/10.1038/s41420-024-02012-4Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

细胞死亡发现。10308（2024）。https://doi.org/10.1038/s41420-024-02012-4Download引文接收日期：2023年11月28日修订日期：2024年5月3日接受日期：2024年5月7日发布日期：2024年7月3日OI：https://doi.org/10.1038/s41420-024-02012-4Share本文与您共享以下链接的任何人都可以阅读此内容：获取可共享链接对不起，本文目前没有可共享的链接。复制到剪贴板。

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