Guihua Song , Mengmeng Sun , Yan Zhang , Bingxue Zhang , Minghao Peng , Beibei Bao
{"title":"LZTFL1 敲除对 OVA 诱导的哮喘小鼠的抗炎作用:通过 ERK/GATA3 信号通路","authors":"Guihua Song , Mengmeng Sun , Yan Zhang , Bingxue Zhang , Minghao Peng , Beibei Bao","doi":"10.1016/j.molimm.2024.01.010","DOIUrl":null,"url":null,"abstract":"<div><p><span><span><span>Asthma is a common chronic respiratory disease characterized by Th2-type inflammation in the airways. </span>Leucine zip transcription factor-like 1 (LZTFL1) has been implicated in the regulation of Th2-related factors. The knockdown of LZTFL1 resulted in decreased levels of IL-4, IL-5, and IL-13. We hypothesize that LZTFL1 may have an effect on asthma. We established an acute asthmatic mouse model using the </span>Ovalbumin (OVA) sensitization, and we found that LZTFL1 expression was upregulated in OVA-induced CD4 + T cells. Mice challenged with OVA were administered 5 × 10</span><sup>7</sup><span><span><span> TU of lentivirus<span> via tail vein injection. LZTFL1 knockdown reversed the frequency of sneezing and nose rubbing in OVA mice. LZTFL1 knockdown reduced </span></span>inflammatory cell<span><span> infiltration, reduced goblet cell<span> numbers, and mitigated collagen deposition in lung tissue. LZTFL1 knockdown decreased the levels of OVA-specific IgE, IL-4, IL-5, and IL-13 in alveolar lavage fluid<span> of asthmatic mice. Furthermore, LZTFL1 knockdown inhibited the aberrant activation of MEK/ERK signaling pathway in asthmatic mice. GATA binding </span></span></span>protein 3<span> (GATA3) is an essential transcription factor in Th2 differentiation. Flow cytometry results revealed that LZTFL1 knockdown reduced the number of GATA3 + CD4 + Th2 cells, while it did not affect the stability of GATA3 mRNA. This may be attributed to ERK signaling which stabilized GATA3 by preventing its </span></span></span>ubiquitination and subsequent degradation. In conclusion, LZTFL1 knockdown attenuates inflammation and pathological changes in OVA-induced asthmatic mice through ERK/GATA3 signaling pathway.</span></p></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":null,"pages":null},"PeriodicalIF":3.2000,"publicationDate":"2024-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Anti-inflammation of LZTFL1 knockdown in OVA-induced asthmatic mice: Through ERK/GATA3 signaling pathway\",\"authors\":\"Guihua Song , Mengmeng Sun , Yan Zhang , Bingxue Zhang , Minghao Peng , Beibei Bao\",\"doi\":\"10.1016/j.molimm.2024.01.010\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p><span><span><span>Asthma is a common chronic respiratory disease characterized by Th2-type inflammation in the airways. </span>Leucine zip transcription factor-like 1 (LZTFL1) has been implicated in the regulation of Th2-related factors. The knockdown of LZTFL1 resulted in decreased levels of IL-4, IL-5, and IL-13. We hypothesize that LZTFL1 may have an effect on asthma. We established an acute asthmatic mouse model using the </span>Ovalbumin (OVA) sensitization, and we found that LZTFL1 expression was upregulated in OVA-induced CD4 + T cells. Mice challenged with OVA were administered 5 × 10</span><sup>7</sup><span><span><span> TU of lentivirus<span> via tail vein injection. LZTFL1 knockdown reversed the frequency of sneezing and nose rubbing in OVA mice. LZTFL1 knockdown reduced </span></span>inflammatory cell<span><span> infiltration, reduced goblet cell<span> numbers, and mitigated collagen deposition in lung tissue. LZTFL1 knockdown decreased the levels of OVA-specific IgE, IL-4, IL-5, and IL-13 in alveolar lavage fluid<span> of asthmatic mice. Furthermore, LZTFL1 knockdown inhibited the aberrant activation of MEK/ERK signaling pathway in asthmatic mice. GATA binding </span></span></span>protein 3<span> (GATA3) is an essential transcription factor in Th2 differentiation. Flow cytometry results revealed that LZTFL1 knockdown reduced the number of GATA3 + CD4 + Th2 cells, while it did not affect the stability of GATA3 mRNA. This may be attributed to ERK signaling which stabilized GATA3 by preventing its </span></span></span>ubiquitination and subsequent degradation. In conclusion, LZTFL1 knockdown attenuates inflammation and pathological changes in OVA-induced asthmatic mice through ERK/GATA3 signaling pathway.</span></p></div>\",\"PeriodicalId\":18938,\"journal\":{\"name\":\"Molecular immunology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2024-02-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S016158902400018X\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular immunology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S016158902400018X","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
哮喘是一种常见的慢性呼吸道疾病,其特征是气道中的 Th2 型炎症。亮氨酸拉链转录因子样 1(LZTFL1)与 Th2 相关因子的调控有关。敲除 LZTFL1 会导致 IL-4、IL-5 和 IL-13 水平下降。我们假设 LZTFL1 可能对哮喘有影响。我们利用卵清蛋白(OVA)致敏法建立了急性哮喘小鼠模型,并发现 LZTFL1 在 OVA 诱导的 CD4 + T 细胞中表达上调。我们发现 LZTFL1 在 OVA 诱导的 CD4 + T 细胞中表达上调。LZTFL1 基因敲除可逆转 OVA 小鼠打喷嚏和揉鼻子的频率。LZTFL1 基因敲除可减少炎症细胞浸润、减少鹅口疮细胞数量并减轻肺组织中的胶原沉积。LZTFL1 基因敲除降低了哮喘小鼠肺泡灌洗液中 OVA 特异性 IgE、IL-4、IL-5 和 IL-13 的水平。此外,LZTFL1敲除抑制了哮喘小鼠体内MEK/ERK信号通路的异常激活。GATA结合蛋白3(GATA3)是Th2分化过程中必不可少的转录因子。流式细胞术结果显示,LZTFL1敲除减少了GATA3 + CD4 + Th2细胞的数量,但并不影响GATA3 mRNA的稳定性。这可能是由于ERK信号通过阻止GATA3的泛素化和随后的降解而稳定了GATA3。总之,LZTFL1敲除可通过ERK/GATA3信号通路减轻OVA诱导的哮喘小鼠的炎症和病理变化。
Anti-inflammation of LZTFL1 knockdown in OVA-induced asthmatic mice: Through ERK/GATA3 signaling pathway
Asthma is a common chronic respiratory disease characterized by Th2-type inflammation in the airways. Leucine zip transcription factor-like 1 (LZTFL1) has been implicated in the regulation of Th2-related factors. The knockdown of LZTFL1 resulted in decreased levels of IL-4, IL-5, and IL-13. We hypothesize that LZTFL1 may have an effect on asthma. We established an acute asthmatic mouse model using the Ovalbumin (OVA) sensitization, and we found that LZTFL1 expression was upregulated in OVA-induced CD4 + T cells. Mice challenged with OVA were administered 5 × 107 TU of lentivirus via tail vein injection. LZTFL1 knockdown reversed the frequency of sneezing and nose rubbing in OVA mice. LZTFL1 knockdown reduced inflammatory cell infiltration, reduced goblet cell numbers, and mitigated collagen deposition in lung tissue. LZTFL1 knockdown decreased the levels of OVA-specific IgE, IL-4, IL-5, and IL-13 in alveolar lavage fluid of asthmatic mice. Furthermore, LZTFL1 knockdown inhibited the aberrant activation of MEK/ERK signaling pathway in asthmatic mice. GATA binding protein 3 (GATA3) is an essential transcription factor in Th2 differentiation. Flow cytometry results revealed that LZTFL1 knockdown reduced the number of GATA3 + CD4 + Th2 cells, while it did not affect the stability of GATA3 mRNA. This may be attributed to ERK signaling which stabilized GATA3 by preventing its ubiquitination and subsequent degradation. In conclusion, LZTFL1 knockdown attenuates inflammation and pathological changes in OVA-induced asthmatic mice through ERK/GATA3 signaling pathway.
期刊介绍:
Molecular Immunology publishes original articles, reviews and commentaries on all areas of immunology, with a particular focus on description of cellular, biochemical or genetic mechanisms underlying immunological phenomena. Studies on all model organisms, from invertebrates to humans, are suitable. Examples include, but are not restricted to:
Infection, autoimmunity, transplantation, immunodeficiencies, inflammation and tumor immunology
Mechanisms of induction, regulation and termination of innate and adaptive immunity
Intercellular communication, cooperation and regulation
Intracellular mechanisms of immunity (endocytosis, protein trafficking, pathogen recognition, antigen presentation, etc)
Mechanisms of action of the cells and molecules of the immune system
Structural analysis
Development of the immune system
Comparative immunology and evolution of the immune system
"Omics" studies and bioinformatics
Vaccines, biotechnology and therapeutic manipulation of the immune system (therapeutic antibodies, cytokines, cellular therapies, etc)
Technical developments.