Molecular immunology最新文献_第3页

Total free lipids from MDR strain of Mycobacterium tuberculosis “M” reduce T cell activation and CTL activity in healthy individuals MDR结核分枝杆菌“M”株总游离脂质降低健康个体T细胞活化和CTL活性

IF 3.2 3区医学

Molecular immunology Pub Date : 2025-05-17 DOI: 10.1016/j.molimm.2025.05.007

María Mercedes Bigi , Belén Imperiale , Marcelo Soria , Beatriz López , Fabiana Bigi , Silvia de la Barrera

{"title":"Total free lipids from MDR strain of Mycobacterium tuberculosis “M” reduce T cell activation and CTL activity in healthy individuals","authors":"María Mercedes Bigi , Belén Imperiale , Marcelo Soria , Beatriz López , Fabiana Bigi , Silvia de la Barrera","doi":"10.1016/j.molimm.2025.05.007","DOIUrl":"10.1016/j.molimm.2025.05.007","url":null,"abstract":"<div><div>Increasing evidence highlights the role of cell wall components in the effectiveness of different <em>Mycobacterium tuberculosis</em> (<em>Mtb)</em> strains in modulating host immune response. We previously demonstrated that the outbreak multidrug-resistant strain M displays a distinctive lipid profile in its cell envelope compared to the closely related sporadic strain 410. Both strains markedly differ in their ability to induce fully functional CD8<sup>+</sup> T cells because of low CD69 signaling and impaired CD4<sup>+</sup> T cell help. In this study, we evaluated the impact of extractable lipids (LP) from M (LP-M) and 410 (LP-410) on the activation and functionality of T cells from healthy individuals. PBMCs were cultured alone or with <em>Mtb</em> in the presence or absence of LP-M, LP-410, or LP from CD1551 mutants in polymorphic genes between M and 410. Then, surface CD69 and intracytoplasmic IL-2 (after 3 days of culture), as well as surface CD107 expression (after 6 days of culture) were determined in T cells by flow cytometry. In contrast to LP-410, LP-M induced low expression of CD69 and IL-2 in CD4<sup>+</sup>/CD8<sup>+</sup> cells and of CD107 in CD8<sup>+</sup> cells. Besides, LP from <em>Mtb</em> strains mutated in <em>Rv1861c</em> and <em>Rv3787c</em> genes inhibited H37Rv-induced T cell response without causing cell death. Thus, our results suggest that LP-M likely through mutations in <em>Rv1861</em> and <em>Rv3787c,</em> inhibits the activation and functionality of T cells from PPD+ healthy human donors and might partially contribute to the development of immune evasion mechanisms in the M strain.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"183 ","pages":"Pages 182-193"},"PeriodicalIF":3.2,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144071271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The m6A demethylase FTO controls Th1 differentiation and immunity against infections m6A去甲基化酶FTO控制Th1分化和对感染的免疫

IF 3.2 3区医学

Molecular immunology Pub Date : 2025-05-15 DOI: 10.1016/j.molimm.2025.05.004

Zhihong Yao , Lina Sun , Yang Gao , Yanhong Su , Boxiao He , Yao Ge , Chen Yang , Xiaoxuan Jia , Anjun Jiao , Chenming Sun , Baojun Zhang

{"title":"The m6A demethylase FTO controls Th1 differentiation and immunity against infections","authors":"Zhihong Yao , Lina Sun , Yang Gao , Yanhong Su , Boxiao He , Yao Ge , Chen Yang , Xiaoxuan Jia , Anjun Jiao , Chenming Sun , Baojun Zhang","doi":"10.1016/j.molimm.2025.05.004","DOIUrl":"10.1016/j.molimm.2025.05.004","url":null,"abstract":"<div><div>Antigen-specific effector CD4<sup>+</sup> T cells are critical for defense against exogenous pathogens. However, the epigenetic mechanisms underlying CD4<sup>+</sup> T cell immune responses, particularly RNA modifications, remain incompletely understood. In this study, we employed a T cell-specific deletion of the fat mass and obesity-associated protein (FTO), a key N6-methyladenosine (m<sup>6</sup>A) demethylase, to elucidate its role in CD4<sup>+</sup> T cell mediated immunity. Our findings demonstrate that FTO is essential for maintaining CD4<sup>+</sup> T cell immune responses and protective functions. Specifically, FTO deficiency restricts the expansion of CD4<sup>+</sup> T helper (Th)1 effector cells following antigen challenge and results in decreased expression of T-bet and IFN-γ in Th1 cells. Additionally, FTO deficient CD4<sup>+</sup> T cells exhibit impaired pathogen elimination. Collectively, our study reveals a novel epigenetic regulatory mechanism in supporting CD4<sup>+</sup> T cell differentiation, providing new insights into the post-transcriptional regulation of CD4<sup>+</sup> T cell immunity and highlighting the potential for therapeutic strategies.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"183 ","pages":"Pages 172-181"},"PeriodicalIF":3.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144068150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeted p38 mitogen-activated protein kinase inhibition potently augment inflammatory responses of human macrophages toward Staphylococcus aureus 靶向p38丝裂原活化蛋白激酶抑制可增强人巨噬细胞对金黄色葡萄球菌的炎症反应

IF 3.2 3区医学

Molecular immunology Pub Date : 2025-05-14 DOI: 10.1016/j.molimm.2025.05.010

Astrid Lund , David Moffat , Stine Dam Jepsen , Claus Desler , Lars Andresen , Søren Bregenholt , Venkat Reddy , Søren Skov

{"title":"Targeted p38 mitogen-activated protein kinase inhibition potently augment inflammatory responses of human macrophages toward Staphylococcus aureus","authors":"Astrid Lund , David Moffat , Stine Dam Jepsen , Claus Desler , Lars Andresen , Søren Bregenholt , Venkat Reddy , Søren Skov","doi":"10.1016/j.molimm.2025.05.010","DOIUrl":"10.1016/j.molimm.2025.05.010","url":null,"abstract":"<div><div>Antibiotic-resistant <em>Staphylococcus aureus (S. aureus)</em> is a growing challenge for human health and novel treatment options are needed. Here we examine a novel therapeutic approach against persistent <em>S. aureus</em> infections based on monocyte/macrophage specific inhibition of the p38α mitogen-activated protein kinase activity. Since systemic p38α kinase inhibition cause aberrant toxicity, we used the myeloid specific p38α kinase inhibitor, MPL-5821. P38α kinase inhibition caused a potent increase in the pro-inflammatory profile of human macrophages after exposure to <em>S. aureus</em>, including upregulation of M1-markers and induction of pro-inflammatory cytokines including IFN-γ, TNF-α, IL-1β, IL12p70, IL-6 and IL-8, as well as an increase in phagocytic capacities. These pro-inflammatory signals were only seen after combined <em>S. aureus</em> exposure and p38α inhibition. Macrophages are often regulated by changes in intracellular metabolism. In agreement with this, the combination of <em>S. aureus</em> exposure and p38α inhibition led to specific changes in glycolytic and mitochondrial activity within the responding macrophages. Our study thus unravels a novel and specific activation of macrophages that augment their response toward <em>S. aureus</em>, without causing aberrant inflammation. This constitutes a unique non-antibiotic therapeutic approach that can potentially be used against persistent <em>S. aureus</em> infection.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"183 ","pages":"Pages 145-155"},"PeriodicalIF":3.2,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143942416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cordycepin ameliorates high glucose-induced proliferation, inflammation, and extracellular matrix deposition in glomerular mesangial cells through Smad7-dependent manner 虫草素通过smad7依赖的方式改善高糖诱导的肾小球系膜细胞的增殖、炎症和细胞外基质沉积

IF 3.2 3区医学

Molecular immunology Pub Date : 2025-05-14 DOI: 10.1016/j.molimm.2025.05.011

Weiyu Han , Shuang Chen , Beiting Ma , Zhewen Deng , Jiaqi Li , Chenglun Tang , Zhengxin Lu , Shanshan Li , Qi Zhang , Bo Ma

{"title":"Cordycepin ameliorates high glucose-induced proliferation, inflammation, and extracellular matrix deposition in glomerular mesangial cells through Smad7-dependent manner","authors":"Weiyu Han , Shuang Chen , Beiting Ma , Zhewen Deng , Jiaqi Li , Chenglun Tang , Zhengxin Lu , Shanshan Li , Qi Zhang , Bo Ma","doi":"10.1016/j.molimm.2025.05.011","DOIUrl":"10.1016/j.molimm.2025.05.011","url":null,"abstract":"<div><div>Diabetic nephropathy (DN) is one of the most common causes of end-stage renal disease. The extracellular matrix deposition is potent pathogenic factors of renal fibrosis and injury. Cordycepin (Cor), a natural nucleoside compound from <em>Cordyceps militaris</em>, has been demonstrated reno-protective properties. Nevertheless, the role and underlying mechanism of Cor in DN have not been studied extensively. This study aimed to investigate the renal protective effects and mechanism of Cor on diabetic mouse models and high glucose (HG) induced-mouse glomerular mesangial cells (GMCs). The results of the biochemical indicators indicated that Cor could ameliorate renal dysfunction, as evidenced by reductions in serum creatinine, blood urea nitrogen, and urinary protein. Histological evaluation further confirmed that Cor ameliorated renal pathological changes, including mesangial matrix expansion, glomerular basement membrane thickening, glomerulosclerosis, and fibrillar collagen deposition. Additionally, Cor alleviated cell proliferation and fibrosis induced by high glucose in GMCs. Mechanistically, Cor upregulated the expression of Smad7, suppressed TGF-β/Smad pathway activation and its downstream NOX4-mediated NLRP3 inflammasome. Furthermore, knockdown of Smad7 by shRNA transfection abrogated the inhibiting effects of Cor in high glucose-induced GMCs. These findings suggested that Cor represented a promising therapeutic candidate for mitigating renal damage in diabetic nephropathy. The underlying mechanism involved the enhancement of Smad7 expression, which in turn suppresses TGF-β/Smad signaling and NOX4-mediated NLRP3 inflammasome activation.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"183 ","pages":"Pages 156-171"},"PeriodicalIF":3.2,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143947186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Phillyrin for sepsis-related acute lung injury: A potential strategy suppressing GSK-3β philyrin治疗败血症相关急性肺损伤：抑制GSK-3β的潜在策略

IF 3.2 3区医学

Molecular immunology Pub Date : 2025-05-12 DOI: 10.1016/j.molimm.2025.04.017

Guangli Yang , Weifu Tan , Lijun Yan , Qiaocong Lao , Wujuan Zheng , Hongyan Ding , Jingtao Yu , Yong Liu , Liyi Zou , Maorun Guo , Linzhong Yu , Xiangjun Zhou , Wei Li , Liling Yang

{"title":"Phillyrin for sepsis-related acute lung injury: A potential strategy suppressing GSK-3β","authors":"Guangli Yang , Weifu Tan , Lijun Yan , Qiaocong Lao , Wujuan Zheng , Hongyan Ding , Jingtao Yu , Yong Liu , Liyi Zou , Maorun Guo , Linzhong Yu , Xiangjun Zhou , Wei Li , Liling Yang","doi":"10.1016/j.molimm.2025.04.017","DOIUrl":"10.1016/j.molimm.2025.04.017","url":null,"abstract":"<div><div>The efficacy of clinical drugs for acute lung injury/acute respiratory distress syndrome (ALI/ARDS) remains suboptimal. Phillyrin (PHN), a compound derived from Forsythia, is believed to alleviate sepsis-related ALI/ARDS; however, its mechanisms are not fully elucidated. In this study, we screened 8331 target genes associated with ALI/ARDS from public databases and identified six hub genes relevant to PHN treatment: AKT1, GSK-3β, PPP2CA, PPP2CB, PPP2R1A, and AR. Receiver operating characteristic analysis and single-cell sequencing analysis revealed the expression of AKT1, GSK-3β, PPP2CA, PPP2CB, and PPP2R1A were markedly elevated. Molecular docking and dynamics simulations indicated that PHN forms a structurally stable complex with glycogen synthase kinase-3β (GSK-3β). Mendelian randomization analyses suggested that PHN, as a potent GSK-3β inhibitor, may promote M2 macrophage polarization and reduce neutrophil recruitment. We validated these findings through in vivo and in vitro experiments, demonstrating that PHN lowers iNOS levels and raises MMR levels by downregulating GSK-3β mRNA expression and protein activity during lipopolysaccharide (LPS)-induced macrophage inflammation. Additionally, PHN inhibited GSK-3β mRNA expression and protein activity, reducing NF-κB-p65 nuclear translocation in LPS-induced zebrafish inflammation and mice ALI. This inhibition decreased levels of TNF-α and IL-6, increased IL-10 levels, promoted M2 macrophage polarization, suppressed neutrophil recruitment, and ultimately ameliorated ALI/ARDS. In conclusion, our results indicate that PHN effectively alleviates LPS-induced ALI/ARDS by suppressing GSK-3β signaling.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"183 ","pages":"Pages 115-136"},"PeriodicalIF":3.2,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143934904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Truncated IFI16 mRNA transcripts can control its viral DNA defense activity 截断的IFI16 mRNA转录物可以控制其病毒DNA防御活性

IF 3.2 3区医学

Molecular immunology Pub Date : 2025-05-12 DOI: 10.1016/j.molimm.2025.05.005

Jorge Martinez-Laso , Isabel Cervera , Marina S. Martinez-Carrasco , Clara Sánchez-Menéndez , Manuel Remesal , Guiomar Casado-Fernández , Elena Mateos , Luis Lemus-Aguilar , Montserrat Torres , Mayte Coiras

{"title":"Truncated IFI16 mRNA transcripts can control its viral DNA defense activity","authors":"Jorge Martinez-Laso , Isabel Cervera , Marina S. Martinez-Carrasco , Clara Sánchez-Menéndez , Manuel Remesal , Guiomar Casado-Fernández , Elena Mateos , Luis Lemus-Aguilar , Montserrat Torres , Mayte Coiras","doi":"10.1016/j.molimm.2025.05.005","DOIUrl":"10.1016/j.molimm.2025.05.005","url":null,"abstract":"<div><div>One of the most well-known viral receptors of the group called named ALRs is IFI16 (interferon-inducible protein 16) that are responsible for responses against viral dsDNA. A pyrin domain (PYD), two HIN domains, a NLS (nuclear localization sequence), and S/T/P repeats region form the structure of IFI16. Five alternatively transcripts have been described (V1, V2, V9, V4 and Vβ) that encode five isoforms (IFI16-iso1, 2, 3, 4 and β) with different structure, localization, and function. Another four transcripts (V3, V5, V6, and V8) and 12 predicted transcripts (VX1-VX7, VX1.1-VX5.1) have also been registered in the Genebank without any structural study. In the present study, we have performed a complete study of the presence of the IFI16 transcripts in a healthy population. All the alternative transcripts described except six of the so-called predicted transcripts were found, furthermore, two new transcripts (V10, V11) were described. The main mechanisms for the regulation of mRNA from IFI16 expression are due to the insertion of non-coding regions and the loss of almost all exons. A total of nine different isoforms were found and the corresponding protein models were constructed to establish the modification of its functionality to form inflammasomes or the binding to viral DNA.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"183 ","pages":"Pages 137-144"},"PeriodicalIF":3.2,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143934905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Gastric cancer cells shuttle lactate to induce inflammatory CAF-like phenotype and function in bone marrow-derived mesenchymal stem cells 胃癌细胞在骨髓间充质干细胞中穿梭乳酸诱导炎症样caf表型和功能

IF 3.2 3区医学

Molecular immunology Pub Date : 2025-05-09 DOI: 10.1016/j.molimm.2025.05.002

Feng Huang , Xiaoli Cao , Jingyu Mei , Chen Wu , Wei Zhu , Li Sun , Chun Dai , Mei Wang

{"title":"Gastric cancer cells shuttle lactate to induce inflammatory CAF-like phenotype and function in bone marrow-derived mesenchymal stem cells","authors":"Feng Huang , Xiaoli Cao , Jingyu Mei , Chen Wu , Wei Zhu , Li Sun , Chun Dai , Mei Wang","doi":"10.1016/j.molimm.2025.05.002","DOIUrl":"10.1016/j.molimm.2025.05.002","url":null,"abstract":"<div><div>Metabolic reprogramming, exemplified by the \"Warburg effect,\" is a hallmark of human cancers, leading to lactate buildup in tumors. Bone marrow-derived mesenchymal stem cells (BM-MSCs), key contributors to cancer-associated fibroblasts (CAFs), integrate into gastric cancer stroma through interactions with cancer cells. However, the role of lactate in activating BM-MSCs in this context remains unclear. Herein, exogenous lactate induced a pro-tumorigenic phenotype in BM-MSCs, which was blocked by AZD3965. Gastric cancer cells released more lactate under hypoxia than normoxia. While normoxic gastric cancer cells could educate BM-MSCs, hypoxic cells were more effective. However, the effects of the supernatant from gastric cancer cells in both conditions were significantly reduced by AZD3965. Similarly, prevention of lactate production by oxamic acid sodium significantly reduced the effects observed. Lactate-activated BM-MSCs showed NF-κB signaling activation, increased IL-8 secretion, and no change in TGF-β signaling. These activated BM-MSCs promoted gastric cancer cell migration and invasion through IL-8 secretion and enhanced resistance to CD8 + T cell cytotoxicity by upregulating PD-L1. Collectively, gastric cancer cells induce an iCAF-like phenotype and function in BM-MSCs through a lactate shuttle mechanism, emphasizing the role of metabolic reprogramming in cellular communication that fosters a supportive tumor microenvironment. Targeting lactate-related pathways may provide new therapeutic strategies to hinder BM-MSCs' supportive roles in gastric cancer.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"183 ","pages":"Pages 93-103"},"PeriodicalIF":3.2,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143927972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Immunotherapeutic efficacy of Th1 stimulatory epitopes derived from Leishmania donovani enolase and triose phosphatase isomerase in experimental visceral leishmaniasis 多诺瓦利什曼烯醇化酶和三糖磷酸酶异构酶衍生的Th1刺激表位对实验性内脏利什曼病的免疫治疗效果

IF 3.2 3区医学

Molecular immunology Pub Date : 2025-05-09 DOI: 10.1016/j.molimm.2025.04.014

Sneha Ratnapriya , Alok K. Yadav , Amogh Anant Sahasrabuddhe , Anuradha Dube

{"title":"Immunotherapeutic efficacy of Th1 stimulatory epitopes derived from Leishmania donovani enolase and triose phosphatase isomerase in experimental visceral leishmaniasis","authors":"Sneha Ratnapriya , Alok K. Yadav , Amogh Anant Sahasrabuddhe , Anuradha Dube","doi":"10.1016/j.molimm.2025.04.014","DOIUrl":"10.1016/j.molimm.2025.04.014","url":null,"abstract":"<div><div>Visceral leishmaniasis is a lethal systemic disease which cannot be controlled by drugs alone given asymptomatic reservoirs and must include alternatives to modulate immune responses of the endemic contacts. Our previous studies have yielded potential immunomodulatory proteins by proteomic approach and their peptides showed significant immunomodulation and prophylactic efficacies. The current study has been intended to evaluate immunotherapeutic potential of the lead peptides (P10, P14 and P15) and their combinations with BCG as adjuvant. Results indicated P10 + 14 as well as P10 + P15 to be the most potential therapeutic peptides cocktails as both these combinations reduced parasite burden by > 65 % eliciting remarkable cellular response. High level of IFN-γ, TNF-α and IL-12 with decreased TGF-β expression suggested skewing of immune response towards Th1 type. These results were further supported by strong DTH and lymphoproliferative responses indicating therapeutic potential of the peptide combinations and possibilities in Kala-azar elimination program.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"183 ","pages":"Pages 104-114"},"PeriodicalIF":3.2,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143927973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Knockdown of RRBP1 regulates endoplasmic reticulum stress to mitigate malignant progression and suppress bortezomib resistance of multiple myeloma cells by inhibiting GRP78 expression 下调RRBP1可调节内质网应激，通过抑制GRP78的表达，减缓恶性进展，抑制多发性骨髓瘤细胞对硼替佐米的耐药性

IF 3.2 3区医学

Molecular immunology Pub Date : 2025-05-08 DOI: 10.1016/j.molimm.2025.05.001

Jie Wang , Haipeng Jia , Sulong Lv, Xiaofen Zhang, Yanchao Duan

{"title":"Knockdown of RRBP1 regulates endoplasmic reticulum stress to mitigate malignant progression and suppress bortezomib resistance of multiple myeloma cells by inhibiting GRP78 expression","authors":"Jie Wang , Haipeng Jia , Sulong Lv, Xiaofen Zhang, Yanchao Duan","doi":"10.1016/j.molimm.2025.05.001","DOIUrl":"10.1016/j.molimm.2025.05.001","url":null,"abstract":"<div><h3>Background</h3><div>Ribosome binding protein 1 (RRBP1) was reported to play a regulatory role in certain cancers. It was related to poor prognosis and drug resistance in multiple myeloma (MM), but its mechanism has not been reported before. Hence, its effect and the specific mechanism on MM cells were explored.</div></div><div><h3>Methods</h3><div>The expression levels of RRBP1 and Glucose-regulated protein 78 (GRP78) in MM tissues were detected by immunohistochemical assay. The expression levels of mRNA and protein were analyzed by qRT-PCR and western blot, respectively. MM cell viability and proliferation were tested by CCK-8 assay. Flow cytometry was used to detect cell apoptosis. Transwell assay was carried out to explore cell migration and invasion.</div></div><div><h3>Results</h3><div>The expression levels of RRBP1 and GRP78 were upregulated in MM tissues and MM cells. Transfection of sh-RRBP1 weakened the proliferation, migration and invasion abilities of MM cells. Knockdown of RRBP1 dropped GRP78 expression and diminished endoplasmic reticulum stress in MM cells. Moreover, Tunicamycin-induced apoptosis of MM cells was enhanced by RRBP1 knockdown. Compared to the control group, inhibition of RRBP1 expression increased the drug sensitivity of bortezomib-resistant MM cells. In addition, overexpression of GRP78 partially repealed the effectiveness of sh-RRBP1 on MM cells.</div></div><div><h3>Conclusion</h3><div>Our study elucidated the inhibitory effect of RRBP1 knockdown on MM cells, which suggested that RRBP1 might be a novel target for the therapy against MM.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"183 ","pages":"Pages 72-82"},"PeriodicalIF":3.2,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143918171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Anti-inflammatory properties of Pleione bulbocodioides extract through STING/ NF-κB pathway inhibition 苦参提取物抑制STING/ NF-κB通路的抗炎作用

IF 3.2 3区医学

Molecular immunology Pub Date : 2025-05-08 DOI: 10.1016/j.molimm.2025.04.015

Jinlei Yun , Yindi Zhang , Hongyan Zhang , Fengkun Xiao , Yichun Wang , Peng Xu , Liping Qu

{"title":"Anti-inflammatory properties of Pleione bulbocodioides extract through STING/ NF-κB pathway inhibition","authors":"Jinlei Yun , Yindi Zhang , Hongyan Zhang , Fengkun Xiao , Yichun Wang , Peng Xu , Liping Qu","doi":"10.1016/j.molimm.2025.04.015","DOIUrl":"10.1016/j.molimm.2025.04.015","url":null,"abstract":"<div><div>The members of <em>Pleione</em> (Orchidaceae) are popular worldwide for their ornamental appeal and medicinal properties. <em>Pleione bulbocodioides</em>, a CITES Appendix II-listed species, has been traditionally used in dermatological therapies but remains pharmacologically understudied. In this study, the in vitro anti-inflammatory effects of extracts from artificially cultivated <em>P. bulbocodioides</em> were investigated. We found the <em>P. bulbocodioides</em> extract (PE) significantly suppressed TNF-α/IFN-γ-induced expression of IL-6, IL-1β, CCL5, CCL8, CXCL8, CXCL3, and TMEM173 (STING) genes in both HaCaT cells and NHEKs. Transcriptomic analysis and Western blotting confirmed the inhibitory effects on STING/NF-κB signaling pathway of PE. And phytochemical characterization identified militarine and batatasin III as principal bioactive constituents responsible for STING/NF-κB pathway inhibition by PE. PE also demonstrated comparable anti-inflammatory efficacy in LPS-induced RAW 264.7 macrophages and SLS-irritated 3D reconstructed human epidermis. Thus, these findings indicate the potential of PE as a natural anti-inflammatory therapeutic or skincare ingredient for dermatological applications.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"183 ","pages":"Pages 83-92"},"PeriodicalIF":3.2,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143923545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0