Immunobiology最新文献

{"title":"Identification and validation of basic fibroblast growth factor as a prognostic biomarker for the response of lung adenocarcinoma patients to bevacizumab treatment","authors":"Hongtao Jiang,&nbsp;Ce Li,&nbsp;Qiang Gong,&nbsp;Hailing Qie","doi":"10.1016/j.imbio.2023.152764","DOIUrl":"10.1016/j.imbio.2023.152764","url":null,"abstract":"<div><p>Basic fibroblast growth factor (bFGF) stimulates angiogenesis, influencing the proliferation, migration, and survival of tumour cells, which have pivotal roles in tumour progression. This study investigated the prognostic significance of bFGF expression in lung adenocarcinoma treated with bevacizumab. The expression levels of bFGF were assessed in bevacizumab-treated patients with lung adenocarcinoma using immunohistochemistry. Propensity score matching (PSM) analysis was performed to evaluate prognostic potential. bFGF expression was also investigated in another independent cohort of patients with lung adenocarcinoma treated with routine<!--> <!-->chemotherapy. We also compared the PSM value of bFGF expression levels independently and in combination with epidermal growth factor receptor and vascular<!--> <!-->endothelial growth factor expression levels. A high bFGF expression level was found to be an independent prognostic factor for disease-free survival in patients receiving bevacizumab-based chemotherapy. Similar results were not observed in patients who underwent routine<!--> <!-->chemotherapy. In conclusion, the bFGF expression level may be a clinically feasible prognostic marker and bFGF is a potential therapeutic target for patients with lung adenocarcinoma receiving routine<!--> <!-->chemotherapy.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"228 6","pages":"Article 152764"},"PeriodicalIF":2.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298523045667/pdfft?md5=b61c9789afb0134764914a47922e5238&pid=1-s2.0-S0171298523045667-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138477589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Baicalein promotes the microglia M2 polarization and suppresses apoptosis by targeting HMOX1/PDE4D to alleviate Alzheimer’s disease","authors":"Qingmei Gong ,&nbsp;Yanbo Wang ,&nbsp;Xiaowei Wang ,&nbsp;Haiyan Pan ,&nbsp;Ci Yan","doi":"10.1016/j.imbio.2023.152761","DOIUrl":"https://doi.org/10.1016/j.imbio.2023.152761","url":null,"abstract":"<div><p><span>Alzheimer's disease (AD) is a neurodegenerative disorder that has quickly becoming one of the most expensive, lethal, and burdening diseases of this century. In the past twenty years, hundreds of </span>drugs<span><span><span> have been tested while only several have been authorized by FDA for AD treatment, hence, searching for candidate agent with therapeutic potential for AD is imminent. Controlling polarization direction of microglia<span> is crucial in AD therapy. Recent research suggests that baicalein<span> has potential to reduce neuroinflammation and prevent </span></span></span>neurodegenerative diseases<span><span> by affecting microglia, while the specific molecular mechanism of baicalein in regulating microglia in the treatment of AD is still unclear. In this study, we investigated how baicalein affected microglial polarization in AD and potential biological mechanisms. In cell experiments, it was verified that baicalein significantly shifted the BV-2 microglia phenotype from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype, inhibited the microglial </span>apoptosis and pro-inflammatory factors, promoted the microglial </span></span>Aβ<span><span><span><span> uptake and anti-inflammatory factors after LPS stimulated. In APP/PS1 mice, it was found that baicalein decreased the Aβ plaque deposition in brain, attenuated NLRP3 inflammasome activation and </span>neuronal apoptosis in APP/PS1 mice. Furthermore, bioinformatics analysis and experiment validated that </span>HMOX1 is a target of baicalein, and we elucidated that baicalein modulated the microglial polarization to inhibit neuroinflammation and </span>neural injury through targeting on the HMOX1/PDE4D axis in AD. In conclusion, our findings indicate the therapeutic effect of baicalein for AD, and baicalein might serve a potential agent for AD treatment.</span></span></p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"228 6","pages":"Article 152761"},"PeriodicalIF":2.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138436986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell transcriptional gene signature analysis identifies IL-17 signaling pathway as the key pathway in sepsis","authors":"Huayan Zhao ,&nbsp;Yuanzhe Li ,&nbsp;Guiying Sun ,&nbsp;Ming Cheng ,&nbsp;Xianfei Ding ,&nbsp;Kun Wang","doi":"10.1016/j.imbio.2023.152763","DOIUrl":"https://doi.org/10.1016/j.imbio.2023.152763","url":null,"abstract":"<div><p><span>Sepsis is a multiple dysregulated systemic inflammatory response with high mortality and leads to public concern. This study was designed to identify possible critical pathways associated with sepsis clinical severity and outcome, which offer potential biomarkers and therapeutic targets for sepsis diagnosis and treatment<span><span>. Single-cell transcriptome profiles of human peripheral blood mononuclear (PBMC) in the healthy control population and sepsis patients were downloaded from the sepsis database GSE167363 and performed quality control before subsequent analysis. The bulk-RNA sequencing of blood samples in the sepsis-associated databases GSE100159 and GSE133822 was also used to confirm the association between critical pathways and sepsis pathology after processing raw data. We found there was a total of 18 distinct clusters in PBMC of sepsis, which was identified by the t-SNE and UMAP dimension reduction analysis. Meanwhile, the main cell types including B, NK, T, and </span>monocyte<span><span><span> cells were identified via the cell maker website and the “Single R” package cell-type annotation analysis. Subsequently, GO<span> and KEGG enrichment analysis of differential expression genes<span> in each cluster found that DEGs between healthy control and sepsis patients were significantly enriched in the IL-17 signaling pathway in monocyte, NK, and </span></span></span>T cells. Finally, GSE100159 and GSE133822 confirmed IL-17 signaling pathway-associated genes including IL-17R, </span>TRAF6, RELB, </span></span></span>TRAF5<span>, CEBPB<span>, JUNB<span><span>, CXCL1, </span>CXCL3, CXCL8, CXCR1, and CXCR2 were significantly up-regulated in sepsis blood samples compared with the age-matched healthy control population. Taken together, we concluded that the IL-17 signaling pathway serves as a significant potential mechanism of sepsis and provides a promising therapeutic target for sepsis treatment. This research will further deepen our understanding of sepsis development.</span></span></span></p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"228 6","pages":"Article 152763"},"PeriodicalIF":2.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138466762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor-infiltrating lymphocytes, PD-L1, and MMR-deficiency combined characterization may identify subgroups of rectal cancer patients who would benefit from immunotherapy","authors":"Alexandra Giatromanolaki ,&nbsp;Christos Kavazis ,&nbsp;Anastasia G. Gkegka ,&nbsp;Maria Kouroupi ,&nbsp;Alexandra Tsaroucha ,&nbsp;Michael Pitiakoudis ,&nbsp;Michael I. Koukourakis","doi":"10.1016/j.imbio.2023.152756","DOIUrl":"https://doi.org/10.1016/j.imbio.2023.152756","url":null,"abstract":"<div><h3>Introduction</h3><p>Mismatch repair deficiency, immunological fertility, and PD-L1 expression status are key histopathological and molecular features defining tumor responsiveness to immunotherapy and, eventually, prognosis. These were investigated in a series of locally advanced rectal cancer patients treated with postoperative chemotherapy and radiotherapy.</p></div><div><h3>Materials and methods</h3><p>Tumor-infiltrating lymphocyte (TIL) density was assessed in hematoxylin-eosin tissue sections. PD-L1 expression and the expression of MMR proteins (MLH1, PSM2, MSH2, and MSH6) were assessed with immunohistochemistry. Their association with histopathological variables (node involvement and tumor budding) and prognosis was assessed.</p></div><div><h3>Results</h3><p>The TIL-density was significantly higher in the invading tumor front and was inversely related to tumor budding and directly with better overall survival (OS) and distant metastasis-free survival (DMFS) (p = 0.02 and 0.02, respectively). Cancer cell PD-L1 expression was related to high TIL-density (p &lt; 0.01) but not to prognosis, although its overexpression defined a trend for poorer OS in patients with high TIL-density. High PD-L1 expression by stroma infiltrating immune cells was linked with better OS and DMFS (p = 0.007 and 0.001, respectively. MMR deficiency was recorded in 26.2 % of cases, and this was linked with higher TIL-density, but not with prognosis.</p></div><div><h3>Conclusions</h3><p>Dense intratumoral lymphocytic infiltration relates to a better prognosis in rectal cancer, although it is also linked with PD-L1 expression that may adversely modulate the anti-tumor effects of TILs. This latter subgroup of patients (high TIL-density/high cancer cell PD-L1 expression) could be an additional target for anti-PD-1/PD-L1 immunotherapy, along with the established subgroup of MMR deficient patients.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"228 6","pages":"Article 152756"},"PeriodicalIF":2.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92042481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human macrophage immunometabolism regulator (MACIR) in patients with periodontitis","authors":"Karol Serwin ,&nbsp;Małgorzata Kozak ,&nbsp;Małgorzata Mazurek-Mochol ,&nbsp;Katarzyna Piotrowska ,&nbsp;Michał Czerewaty ,&nbsp;Andrzej Pawlik","doi":"10.1016/j.imbio.2023.152760","DOIUrl":"https://doi.org/10.1016/j.imbio.2023.152760","url":null,"abstract":"<div><h3>Objective</h3><p>Periodontitis is a local inflammatory reaction caused by bacterial infection in which immune cells, including macrophages, are involved. Recent studies have shown that an important regulator of macrophage function is the human macrophage immunometabolism regulator (MACIR). This gene has been shown to play a key role in modulating the immune response by affecting the activity of fibroblasts and macrophages.</p><p>In this study, we investigated the expression of MACIR in the gingival tissues of patients with periodontal disease, as well as the effect of IL-1β and TNF-α on the expression of MACIR gene and protein in human gingival fibroblasts.</p></div><div><h3>Methods</h3><p>MACIR mRNA expression in gingival tissue samples was determined using Real-time PCR. Expression of MACIR protein was determined using immunofluorescent staining and western blotting.</p></div><div><h3>Results</h3><p>The MACIR mRNA expression in gingival tissue samples in patients with periodontitis was statistically significantly lower than in gingival tissue samples from healthy controls (p = 0.009). The stimulation of human gingival fibroblasts with IL-1β and TNF-α resulted in a statistically significant decrease of MACIR gene mRNA expression. In western blotting and immunofluorescent analysis, we confirmed that the stimulation of the primary culture of human gingival fibroblasts by both IL-1β and TNF-α decreases the expression of MACIR protein.</p></div><div><h3>Conclusion</h3><p>The results of the study suggest that MACIR is an important regulator of the inflammatory process in patients with periodontitis. Decreased expression of the MACIR gene may activate macrophages to secrete mediators that increase inflammation and cause periodontal tissue destruction.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"228 6","pages":"Article 152760"},"PeriodicalIF":2.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S017129852304562X/pdfft?md5=f08b8b868f96466f53124010bc78db4f&pid=1-s2.0-S017129852304562X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134653483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adipose tissue-derived mesenchymal stromal cells attenuate acute lung injury induced by trauma and haemorrhagic shock","authors":"Zhi Zhang ,&nbsp;Xiaoxia Yang ,&nbsp;Qinghong Meng ,&nbsp;Yiyin Long ,&nbsp;Xiaofeng Shi ,&nbsp;Yuliang Wang","doi":"10.1016/j.imbio.2023.152765","DOIUrl":"https://doi.org/10.1016/j.imbio.2023.152765","url":null,"abstract":"<div><h3>Background</h3><p><span>Mesenchymal stromal cells<span> (MSCs) have shown promising therapeutic options for acute lung injury (ALI) caused by multiple factors. Here, we evaluated the therapeutic potential of adipose tissue-derived mesenchymal stromal cells (ADSCs) in trauma and </span></span>hemorrhagic shock (THS)-induced ALI.</p></div><div><h3>Methods</h3><p><span>ALI model induced by THS was constructed by fractures plus abdominal trauma<span> plus acute hemorrhage plus fluid resuscitation. The ADSCs group rats were generated by injecting 2 × 10</span></span>⁶<span> ADSCs at 0 and 1 h after THS. The sham, ALI, and ADSCs group rats were sacrificed at 24 h after resuscitation. The changes in lung histopathology<span>, total protein in bronchoalveolar lavage fluid (BALF), mRNA expression of pro-inflammatory/anti-inflammatory cytokines, antioxidant, and anti-apoptotic indicator, and the activity of Toll-like receptor 4 (TLR4) signaling in lung tissues were evaluated.</span></span></p></div><div><h3>Results</h3><p>Administration of the ADSCs reversed ALI induced by THS, including lung histopathological changes/scores, and BALF total protein concentration. Additionally, ADSCs therapy also significantly down-regulated mRNA expression of pro-inflammatory TNF-α, IL-1β, and IL-6, up-regulated mRNA expression of anti-inflammatory IL-10, anti-apoptotic molecule Bcl-2, and anti-oxidative molecule HO-1 in THS rats. Furthermore, ADSCs suppressed the expression of TLR4 in lung tissue.</p></div><div><h3>Conclusion</h3><p>Our data show that ADSCs administration can exert therapeutic effects on THS-induced ALI in rats and may provide beneficial in preventative strategies for ALI.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"228 6","pages":"Article 152765"},"PeriodicalIF":2.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138454176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IL-27p28 specifically regulates MHC II expression in macrophages through CIITA","authors":"Yu Han ,&nbsp;Xu Zhang ,&nbsp;Qing Wang ,&nbsp;Xiaoyue Cui ,&nbsp;Hesuiyuan Wang ,&nbsp;Xiang Zhang ,&nbsp;Qian Wang ,&nbsp;Jianbin Ji ,&nbsp;Yuebing Wang ,&nbsp;Shusen Wang ,&nbsp;Xiuming Zhang ,&nbsp;Haijin Xu ,&nbsp;Mingqiang Qiao ,&nbsp;Zhenzhou Wu","doi":"10.1016/j.imbio.2023.152757","DOIUrl":"10.1016/j.imbio.2023.152757","url":null,"abstract":"<div><p>Antigen-presenting cells (APCs) constantly express major histocompatibility complex II (MHC II), including macrophages and dendritic cells (DCs) which deliver antigens to CD4⁺ T cells and play an important role in adaptive immunity. The expression of MHC II is controlled by the transcriptional coactivator CIITA. Interleukin-27 (IL-27), a newly discovered IL-12 family cytokine, is composed of p28 and EBI3 subunits. In this study, we used IL-27p28 conditional knock-out mice to investigate the regulatory effects of IL-27p28 on macrophage polarization and the expression of MHC II in macrophages. We found that MHC II expression was upregulated in the bone marrow-derived and peritoneal exudate macrophages (BMDMs; PEMs) from IL-27p28-deficient mice, with their inflammation regulating function unaffected. We also demonstrated that in the APCs, IL-27p28 selectively regulated MHC II expression in macrophages but not in dendritic cells. During <em>Pseudomonas aeruginosa</em> (<em>P. aeruginosa</em>) reinfection, higher survival rate, bacterial clearance, and ratio of CD4⁺/CD8⁺ T cells in the spleen during the specific immune phase were observed in IL-27p28 defect mice, as well as an increased MHC II expression in alveolar macrophages (AMs). But these did not occur in the first infection. For the first time we discovered that IL-27p28 specifically regulates the expression of MHC II in macrophages by regulating CIITA, while its absence enhances antigen presentation and adaptive immunity against <em>P. aeruginosa</em>.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"228 6","pages":"Article 152757"},"PeriodicalIF":2.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S017129852304559X/pdfft?md5=46dbdc5a781a0e4ade29015fe462da7c&pid=1-s2.0-S017129852304559X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72014158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-inflammatory activity of calmodulin-lysine N-methyltransferase through suppressing the caspase-11 non-canonical inflammasome","authors":"Hui-Jin Cho,&nbsp;Dong Joon Lee,&nbsp;Young-Su Yi","doi":"10.1016/j.imbio.2023.152758","DOIUrl":"10.1016/j.imbio.2023.152758","url":null,"abstract":"<div><p>Calmodulin (CaM)-lysine N-methyltransferase (CAMKMT) is a novel methyltransferase that catalyzes lysine trimethylation in CaM. However, its specific roles in inflammatory responses and diseases remain unclear. In this study, we investigated the effects of CAMKMT on caspase-11 non-canonical inflammasomes. CAMKMT expression levels were significantly decreased during inflammatory responses activated by caspase-11 non-canonical inflammasome in macrophages. Moreover, CaM lysine trimethylation was markedly inhibited, but no change was observed in CaM expression during these inflammatory responses in macrophages. Activation of the CaM downstream effectors, CaM-dependent protein<!--> <!-->kinase kinase 2 and CaM-dependent protein<!--> <!-->kinase type IV, was also inhibited during inflammatory responses activated by caspase-11 non-canonical inflammasome in macrophages. Notably, forced expression of CAMKMT restrained caspase-11 non-canonical inflammasome activation via inhibiting proteolytic activation of caspase-11 and gasdermin D (GSDMD), which in turn suppressed pyroptosis and the release of interleukin (IL)-1β and IL-18 in macrophages. Finally, an <em>in vivo</em> study revealed that CAMKMT ameliorated lipopolysaccharide (LPS)-stimulated acute lethal sepsis in mice by increasing the survival rate and reducing the serum levels of IL-1 β. These findings suggest CAMKMT as a novel methyltransferase that plays an anti-inflammatory role through restraining caspase-11 non-canonical inflammasome in macrophages.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"228 6","pages":"Article 152758"},"PeriodicalIF":2.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72209148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of gold nanoparticles (AuNPs) on eosinophils isolated from male and female individuals","authors":"Marion Vanharen,&nbsp;Denis Girard","doi":"10.1016/j.imbio.2023.152762","DOIUrl":"https://doi.org/10.1016/j.imbio.2023.152762","url":null,"abstract":"<div><p><span>It is well established that some differences exist between the male and female immune systems. Despites this, a sex-based analysis is not frequently performed in most scientific published reports. Knowing that inflammation is a common undesired effect observed resulting from nanoparticle<span> (NP) exposure, we investigate here how in vitro treatment<span> of gold NPs with a primary size of 20 and 70 nm (AuNP</span></span></span>₂₀ and AuNP₇₀<span>, respectively) will alter the biology of human eosinophils isolated from men and women blood. We found that treatment of AuNP</span>₇₀, but not AuNP₂₀<span><span>, significantly delay apoptosis only in eosinophils isolated from women. AuNPs were found to decrease eosinophil </span>phagocytosis, however, significance was only observed in AuNP</span>₂₀-induced eosinophils isolated from women. The production of IL-8 was significantly increased in response to both AuNPs but only in eosinophils isolated from men and the production of IL-1β was increased in AuNPs-induced eosinophils, although significance was observed only in AuNP₇₀-induced eosinophils isolated from women. We conclude that future studies investigating the toxicity of AuNPs (or other NPs) should include a sex-based analysis, especially if the tested NPs have potential medical applications knowing the increased interest in the development of personalized precision medicine.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"228 6","pages":"Article 152762"},"PeriodicalIF":2.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138435932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the anti-inflammatory effects of PI3Kδ/γ inhibitors for treating acute lung injury","authors":"Wendian Xiong ,&nbsp;Lei Jia ,&nbsp;Yanfei Cai ,&nbsp;Yun Chen ,&nbsp;Mingzhu Gao ,&nbsp;Jian Jin ,&nbsp;Jingyu Zhu","doi":"10.1016/j.imbio.2023.152753","DOIUrl":"10.1016/j.imbio.2023.152753","url":null,"abstract":"<div><p>Phosphatidylinositol 3-kinase delta (PI3Kδ) and gamma (PI3Kγ) are predominantly located in immune and hematopoietic cells. It is well-established that PI3Kδ/γ plays important roles in the immune system and participates in inflammation; hence, it could be a potential target for anti-inflammatory therapy. Currently, several PI3K inhibitors are used clinically to treat cancers with aberrant PI3K signaling; however, their role in treating acute respiratory inflammatory diseases has rarely been explored. Herein, we investigated the potential anti-inflammatory activities of several pharmacological PI3K inhibitors, including marketed drugs idelalisib (PI3Kδ), duvelisib (PI3Kδ/γ), and copanlisib (pan-PI3K with preferential α/δ) and the clinical drug eganelisib (PI3Kγ), for treating acute lung injury (ALI). In the lipopolysaccharide-induced RAW264.7 macrophage inflammatory model, the four inhibitors significantly suppressed proinflammatory cytokine expression by inhibiting the PI3K signaling pathway. Oral administration of PI3K inhibitors markedly improved lung injury in a murine model of ALI. PI3K pathway inhibition decreased inflammatory cell infiltration and total<!--> <!-->protein levels, as well as reduced the expression of associated lung inflammatory factors. Collectively, all four representative PI3K inhibitors exerted prominent anti-inflammatory properties, indicating that PI3K δ and/or γ inhibition could be ideal targets to treat respiratory inflammatory diseases by reducing the inflammatory response. The findings of the current study provide a new basis for utilizing PI3K inhibitors to treat acute respiratory inflammatory diseases.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"228 6","pages":"Article 152753"},"PeriodicalIF":2.8,"publicationDate":"2023-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41199496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}