Journal of Innate Immunity最新文献_第2页

MDM2 Is Essential to Maintain the Homeostasis of Epithelial Cells by Targeting p53. MDM2 通过靶向 p53 来维持上皮细胞的平衡。

IF 4.7 3区医学

Journal of Innate Immunity Pub Date : 2024-01-01 Epub Date: 2024-08-12 DOI: 10.1159/000539824

Su Wang, Shufen Zhong, Ying Huang, Songling Zhu, Shuangfeng Chen, Ran Wang, Sonam Wangmo, Bo Peng, Houkun Lv, Jichao Yang, Liyan Ma, Zhiyang Ling, Yaguang Zhang, Pengfei Sui, Bing Sun

{"title":"MDM2 Is Essential to Maintain the Homeostasis of Epithelial Cells by Targeting p53.","authors":"Su Wang, Shufen Zhong, Ying Huang, Songling Zhu, Shuangfeng Chen, Ran Wang, Sonam Wangmo, Bo Peng, Houkun Lv, Jichao Yang, Liyan Ma, Zhiyang Ling, Yaguang Zhang, Pengfei Sui, Bing Sun","doi":"10.1159/000539824","DOIUrl":"10.1159/000539824","url":null,"abstract":"Introduction: MDM2 is known as the primary negative regulator of p53, and MDM2 promotes lung cancer fibrosis and lung injury through p53-dependent and p53-independent pathways. However, the mechanism by which MDM2 influences the pathogenesis of asthma is unknown. In this study, we investigated the function of MDM2 in lung epithelial cells in type 2 lung inflammation.Methods: We used type II alveolar epithelial cell-specific heterozygous knockout of Mdm2 mice to validate its function. Then papain-induced asthma model was established, and changes in inflammation were observed by measuring immunohistochemistry and flow cytometry analysis.Results: In this study, we knockdown the mouse Mdm2 gene in type 2 alveolar epithelial cells. We demonstrated that heterozygous Mdm2 gene-deleted mice were highly susceptible to protease allergen papain-induced pulmonary inflammation characterized by increased ILC2 numbers, IL-5 and IL-13 cytokine levels, and lung pathology. A mechanistic study showed that following the decreased expression of Mdm2 in lung epithelial cells and A549 cell line, p53 was overactivated, and the expression of its downstream genes p21, Puma, and Noxa was elevated, which resulted in apoptosis. After Mdm2 knockdown, the mRNA expression of inflammation-related gene IL-25, HMGB1, and TNF-α were increased, which further amplified the downstream ILC2 response and lung inflammation.Conclusion: These results indicate that Mdm2 maintains the homeostasis of lung epithelial cells by targeting P53 and regulates the function of lung epithelial cells under type 2 lung inflammation.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11521410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ehrlichia chaffeensis Co-Opts Phagocytic Hemocytes for Systemic Dissemination in the Lone Star Tick, Amblyomma americanum. 沙弗氏埃利希菌在孤星蜱（Amblyomma americanum）体内共同利用吞噬血细胞进行系统性传播。

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2024-01-01 Epub Date: 2023-12-22 DOI: 10.1159/000535986

Abdulsalam Adegoke, Julia Hanson, Ryan C Smith, Shahid Karim

{"title":"Ehrlichia chaffeensis Co-Opts Phagocytic Hemocytes for Systemic Dissemination in the Lone Star Tick, Amblyomma americanum.","authors":"Abdulsalam Adegoke, Julia Hanson, Ryan C Smith, Shahid Karim","doi":"10.1159/000535986","DOIUrl":"10.1159/000535986","url":null,"abstract":"Introduction: Hematophagous arthropods can acquire and transmit several pathogens of medical importance. In ticks, the innate immune system is crucial in the outcome between vector-pathogen interaction and overall vector competence. However, the specific immune response(s) elicited by the immune cells known as hemocytes remains largely undefined in Ehrlichia chaffeensis and its competent tick vector, Amblyomma americanum.Methods: We utilized injection of clodronate liposome to deplete tick granulocytes combined with infection with E. chaffeensis to demonstrate their essential role in microbial infection.Results: Here, we show that granulocytes, professional phagocytic cells, are integral in eliciting immune responses against commensal and pathogen infection. The chemical depletion of granulocytes led to decreased phagocytic efficiency of tissue-associated hemocytes. We demonstrate that E. chaffeensis can infect circulating hemocytes, and both cell-free plasma and hemocytes from E. chaffeensis-infected ticks can establish Ehrlichia infection in recipient ticks. Lastly, we provide evidence to show that granulocytes play a dual role in E. chaffeensis infection. Depleting granulocytic hemocytes increased Ehrlichia load in the salivary gland and midgut tissues. In contrast, granulocyte depletion led to a reduced systemic load of Ehrlichia.Conclusion: This study has identified multiple roles for granulocytic hemocytes in the control and systemic dissemination of E. chaffeensis infection.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10794049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139032400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TLR9-Dependent Activation by Inactivated Parapoxvirus Ovis in Murine Bone Marrow-Derived Dendritic Cells Is Associated with Specific Strain-Dependent Dendritic Cell Subsets. 在小鼠骨髓树突状细胞中，灭活的副疱疹病毒（iPPVO）对TLR9的依赖性激活与特定毒株依赖性树突状细胞亚群有关。

IF 4.7 3区医学

Journal of Innate Immunity Pub Date : 2024-01-01 Epub Date: 2024-06-08 DOI: 10.1159/000538625

Yanqin Du, Hang Sun, Sonakshi Bhattacharjee, Alexander Birkmann, Ulf Dittmer, Mengji Lu

{"title":"TLR9-Dependent Activation by Inactivated Parapoxvirus Ovis in Murine Bone Marrow-Derived Dendritic Cells Is Associated with Specific Strain-Dependent Dendritic Cell Subsets.","authors":"Yanqin Du, Hang Sun, Sonakshi Bhattacharjee, Alexander Birkmann, Ulf Dittmer, Mengji Lu","doi":"10.1159/000538625","DOIUrl":"10.1159/000538625","url":null,"abstract":"Introduction: Inactivated parapoxvirus ovis (iPPVO) exerts strong immunomodulatory effects on innate immune cells, making it an attractive therapeutic candidate. However, little is known about the signaling pathways that are involved in iPPVO-induced immune responses.Methods: In this study, we systematically analyzed how different types of dendritic cells (DCs) react to iPPVO (Zylexis, strain D1701) in both BALB/c and C57BL/6 mice by flow cytometry and ELISAs, and investigated which signaling pathway is related to DC activation by Western blotting and protein profiling.Results: We demonstrated that bone marrow-derived conventional DCs (BM-cDCs) and bone marrow-derived plasmacytoid DCs (BM-pDCs) matured and secreted type I interferons in response to Zylexis stimulation in both mouse strains. Similarly, Zylexis promoted the secretion of IL-12/23p40 and TNF by pDCs. However, IL-12/23p40 and TNF secretion by cDCs were induced in BALB/c mice but not in C57BL/6 mice. Analyzing the underlying signaling pathways revealed that iPPVO-induced maturation of cDCs was Toll-like receptor 9 (TLR9) independent, while the maturation of pDCs partially depended on the TLR9 pathway. Moreover, the production of proinflammatory cytokines by cDCs and the secretion of IFN-α/β by pDCs partially depended on the TLR9 pathway in both mouse strains. Therefore, other signaling pathways seem to participate in the response of DCs to iPPVO, supported by protein profiling.Conclusion: Our data provide useful insights into the diversity of iPPVO sensors and their varying effects across different strains and species.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11249554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Role of Ficolins in Lung Injury. Ficolins 在肺损伤中的作用

IF 4.7 3区医学

Journal of Innate Immunity Pub Date : 2024-01-01 Epub Date: 2024-08-19 DOI: 10.1159/000540954

Meiyun Zhao, Xiaowu Tan, Xu Wu

{"title":"The Role of Ficolins in Lung Injury.","authors":"Meiyun Zhao, Xiaowu Tan, Xu Wu","doi":"10.1159/000540954","DOIUrl":"10.1159/000540954","url":null,"abstract":"Background: Respiratory diseases seriously threaten human health worldwide, and lung injury is an important component of respiratory disease. Complement activation is an important function of the innate immune system. Complement activation helps the body defend against invasion by external microorganisms, whereas excessive complement activation can exacerbate tissue damage or lead to unwanted side effects. Ficolins are a class of immune-related proteins in the lectin pathway that play important roles in the body's immune defense. Although individual ficolins are not well understood, current information suggests that ficolins may play an important regulatory role in lung injury.Summary: Several studies have shown that ficolins are involved in the immune response in the lung, particularly in the response to infectious and inflammatory processes.Key messages: This review summarizes the role of ficolins in lung injury. Ficolins may influence the development and repair of lung injury by recognizing and binding pathogenic microorganisms, modulating the inflammatory response, and promoting the clearance of immune cells. In addition, ficolins are associated with the development and progression of lung diseases (such as pneumonia and ARDS) and may have an important impact on the pathophysiological processes of inflammatory diseases.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11521482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142006268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Inflammatory Response Induced by Aspergillus fumigatus Conidia Is Dependent on Complement Activation: Insight from a Whole Blood Model. 曲霉菌分生孢子诱导的炎症反应依赖于补体激活--全血模型的启示。

IF 4.7 3区医学

Journal of Innate Immunity Pub Date : 2024-01-01 Epub Date: 2024-05-20 DOI: 10.1159/000539368

Beatrice Fageräng, Maximilian Peter Götz, Leon Cyranka, Corinna Lau, Per H Nilsson, Tom Eirik Mollnes, Peter Garred

{"title":"The Inflammatory Response Induced by Aspergillus fumigatus Conidia Is Dependent on Complement Activation: Insight from a Whole Blood Model.","authors":"Beatrice Fageräng, Maximilian Peter Götz, Leon Cyranka, Corinna Lau, Per H Nilsson, Tom Eirik Mollnes, Peter Garred","doi":"10.1159/000539368","DOIUrl":"10.1159/000539368","url":null,"abstract":"Introduction: We aimed to elucidate the inflammatory response of Aspergillus fumigatus conidia in a whole-blood model of innate immune activation and to compare it with the well-characterized inflammatory reaction to Escherichia coli.Methods: Employing a human lepirudin whole-blood model, we analyzed complement and leukocyte activation by measuring the sC5b-9 complex and assessing CD11b expression. A 27-multiplex system was used for quantification of cytokines. Selective cell removal from whole blood and inhibition of C3, C5, and CD14 were also applied.Results: Our findings demonstrated a marked elevation in sC5b-9 and CD11b post-A. fumigatus incubation. Thirteen cytokines (TNF, IL-1β, IL-1ra, IL-4, IL-6, IL-8, IL-17, IFNγ, MCP-1, MIP-1α, MIP-1β, FGF-basic, and G-CSF) showed increased levels. A generally lower level of cytokine release and CD11b expression was observed with A. fumigatus conidia than with E. coli. Notably, monocytes were instrumental in releasing all cytokines except MCP-1. IL-1ra was found to be both monocyte and granulocyte-dependent. Pre-inhibiting with C3 and CD14 inhibitors resulted in decreased release patterns for six cytokines (TNF, IL-1β, IL-6, IL-8, MIP-1α, and MIP-1β), with minimal effects by C5-inhibition.Conclusion: A. fumigatus conidia induced complement activation comparable to E. coli, whereas CD11b expression and cytokine release were lower, underscoring distinct inflammatory responses between these pathogens. Complement C3 inhibition attenuated cytokine release indicating a C3-level role of complement in A. fumigatus immunity.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11250388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141071264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Analyzing the Role of Specific Damage-Associated Molecular Patterns-Related Genes in Osteoarthritis and Investigating the Association between β-Amyloid and Apolipoprotein E Isoforms. 分析特定损伤相关分子模式相关基因在骨关节炎中的作用并研究β-淀粉样蛋白与载脂蛋白E异构体之间的关联。

IF 4.7 3区医学

Journal of Innate Immunity Pub Date : 2024-01-01 Epub Date: 2024-10-29 DOI: 10.1159/000541542

Fangling Yuan, Yatian Tang, Feifei Zheng, Qipeng Xie

{"title":"Analyzing the Role of Specific Damage-Associated Molecular Patterns-Related Genes in Osteoarthritis and Investigating the Association between β-Amyloid and Apolipoprotein E Isoforms.","authors":"Fangling Yuan, Yatian Tang, Feifei Zheng, Qipeng Xie","doi":"10.1159/000541542","DOIUrl":"10.1159/000541542","url":null,"abstract":"Introduction: Osteoarthritis (OA) is a prevalent chronic joint disorder. It is characterized by an immune response that maintains a low level of inflammation throughout its progression. During OA, cartilage degradation leads to the release of damage-associated molecular patterns (DAMPs), which intensify the inflammatory response. β-Amyloid is a well-recognized DAMP in OA, can interact with APOE isoforms.Methods: This study identified DAMPs-related genes in OA using bioinformatics techniques. Additionally, we examined the expression levels of β-amyloid and apolipoprotein E (ApoE) isoforms by enzyme-linked immunosorbent assay.Results: We identified 10 key genes by machine learning techniques. Immune infiltration analysis revealed upregulation of various immune cell types in OA cartilage, underscoring the critical role of inflammation in OA pathogenesis. In the validation study, elevated serum levels of β-amyloid in knee osteoarthritis (KOA) patients were confirmed, showing positive correlations with ApoE2 and ApoE4. Notably, ApoE3 was identified as an independent protective factor against KOA.Conclusion: In this bioinformatics analysis, we identified the DAMPs-related genes of KOA and explored their potential functions and regulatory networks. The high expression of β-amyloid in KOA was confirmed by experiments, and the correlation between β-amyloid and ApoE2, ApoE4 in KOA was revealed for the first time, this provides a new way to explore the pathogenesis of KOA and to study the therapeutic targets of KOA.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11521507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Roles of Innate Immune Cells in Atopic Dermatitis. 先天性免疫细胞在特应性皮炎中的作用。

IF 4.7 3区医学

Journal of Innate Immunity Pub Date : 2024-01-01 Epub Date: 2024-07-18 DOI: 10.1159/000539534

Yuke Pan, Youyi Wang, Meinian Xu, Meizhen Zhong, Xiaoming Peng, Kang Zeng, Xiaowen Huang

引用次数: 0

Single-Nucleus Sequencing of Silkworm Larval Brain Reveals the Key Role of Lysozyme in the Antiviral Immune Response in Brain Hemocytes. 蚕幼虫脑单核测序揭示了溶菌酶在脑血细胞抗病毒免疫反应中的关键作用。

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2024-01-01 Epub Date: 2024-02-26 DOI: 10.1159/000537815

Min Feng, Shigang Fei, Jinglei Zou, Junming Xia, Wenxuan Lai, Yigui Huang, Luc Swevers, Jingchen Sun

{"title":"Single-Nucleus Sequencing of Silkworm Larval Brain Reveals the Key Role of Lysozyme in the Antiviral Immune Response in Brain Hemocytes.","authors":"Min Feng, Shigang Fei, Jinglei Zou, Junming Xia, Wenxuan Lai, Yigui Huang, Luc Swevers, Jingchen Sun","doi":"10.1159/000537815","DOIUrl":"10.1159/000537815","url":null,"abstract":"Introduction: The brain is considered as an immune-privileged organ, yet innate immune reactions can occur in the central nervous system of vertebrates and invertebrates. Silkworm (Bombyx mori) is an economically important insect and a lepidopteran model species. The diversity of cell types in the silkworm brain, and how these cell subsets produce an immune response to virus infection, remains largely unknown.Methods: Single-nucleus RNA sequencing (snRNA-seq), bioinformatics analysis, RNAi, and other methods were mainly used to analyze the cell types and gene functions of the silkworm brain.Results: We used snRNA-seq to identify 19 distinct clusters representing Kenyon cell, glial cell, olfactory projection neuron, optic lobes neuron, hemocyte-like cell, and muscle cell types in the B. mori nucleopolyhedrovirus (BmNPV)-infected and BmNPV-uninfected silkworm larvae brain at the late stage of infection. Further, we found that the cell subset that exerts an antiviral function in the silkworm larvae brain corresponds to hemocytes. Specifically, antimicrobial peptides were significantly induced by BmNPV infection in the hemocytes, especially lysozyme, exerting antiviral effects.Conclusion: Our single-cell dataset reveals the diversity of silkworm larvae brain cells, and the transcriptome analysis provides insights into the immune response following virus infection at the single-cell level.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10965234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139931524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Macrophage: Hidden Criminal in Therapy Resistance. 巨噬细胞：抗药性的隐形罪犯

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2024-01-01 Epub Date: 2024-03-05 DOI: 10.1159/000538212

Yimin Ding, Qian Cao, Wenjuan Yang, Junjie Xu, Peng Xiao

{"title":"Macrophage: Hidden Criminal in Therapy Resistance.","authors":"Yimin Ding, Qian Cao, Wenjuan Yang, Junjie Xu, Peng Xiao","doi":"10.1159/000538212","DOIUrl":"10.1159/000538212","url":null,"abstract":"Background: Although substantial efforts have been made by researchers to develop drugs, a disappointing reality is that the emergence of drug resistance is an unavoidable reality for the majority of patients. In recent years, emerging evidence suggests a connection between drug resistance and immune dysregulation.Summary: As a ubiquitously distributed, versatile innate immune cell, macrophages play essential roles in maintaining tissue homeostasis in a steady state. Nevertheless, it is becoming aware that macrophages undermine the action of therapeutic drugs across various disease types. Reprogramming macrophage function has been proven to be effective in restoring patient responsiveness to treatment. Herein, we comprehensively reviewed how macrophages respond to drugs and the mechanisms by which they contribute to treatment unresponsiveness in cancer, inflammatory diseases, and metabolic diseases. In addition, future prospects in macrophage-based combination therapy were discussed.Key messages: Targeting macrophages is a promising strategy for overcoming drug resistance in immune disorders.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10990480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140039581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Human Host Defense Peptide LL-37 Suppresses TNFα-Mediated Matrix Metalloproteinases MMP9 and MMP13 in Human Bronchial Epithelial Cells. 人类宿主防御肽 LL-37 可抑制 TNFα 介导的人类支气管上皮细胞基质金属蛋白酶 MMP9 和 MMP13。

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2024-01-01 Epub Date: 2024-03-12 DOI: 10.1159/000537775

Anthony Altieri, Courtney Lynn Marshall, Padmanie Ramotar, Dylan Lloyd, Mahadevappa Hemshekhar, Victor Spicer, Anne M van der Does, Neeloffer Mookherjee

{"title":"Human Host Defense Peptide LL-37 Suppresses TNFα-Mediated Matrix Metalloproteinases MMP9 and MMP13 in Human Bronchial Epithelial Cells.","authors":"Anthony Altieri, Courtney Lynn Marshall, Padmanie Ramotar, Dylan Lloyd, Mahadevappa Hemshekhar, Victor Spicer, Anne M van der Does, Neeloffer Mookherjee","doi":"10.1159/000537775","DOIUrl":"10.1159/000537775","url":null,"abstract":"Introduction: TNFα-inducible matrix metalloproteinases play a critical role in the process of airway remodeling in respiratory inflammatory disease including asthma. The cationic host defense peptide LL-37 is elevated in the lungs during airway inflammation. However, the impact of LL-37 on TNFα-driven processes is not well understood. Here, we examined the effect of LL-37 on TNFα-mediated responses in human bronchial epithelial cells (HBECs).Methods: We used a slow off-rate modified aptamer-based proteomics approach to define the HBEC proteome altered in response to TNFα. Abundance of selected protein candidates and signaling intermediates was examined using immunoassays, ELISA and Western blots, and mRNA abundance was examined by qRT-PCR.Results: Proteomics analysis revealed that 124 proteins were significantly altered, 12 proteins were enhanced by ≥2-fold compared to unstimulated cells, in response to TNFα. MMP9 was the topmost increased protein in response to TNFα, enhanced by ∼10-fold, and MMP13 was increased by ∼3-fold, compared to unstimulated cells. Furthermore, we demonstrated that LL-37 significantly suppressed TNFα-mediated MMP9 and MMP13 in HBEC. Mechanistic data revealed that TNFα-mediated MMP9 and MMP13 production is controlled by SRC kinase and that LL-37 enhances related upstream negative regulators, namely, phospho-AKT (T308) and TNFα-mediated TNFAIP3 or A20.Conclusions: The findings of this study suggest that LL-37 may play a role in intervening in the process of airway remodeling in chronic inflammatory respiratory disease such as asthma.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10997319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140110421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0