Immunobiology最新文献

{"title":"Engagement of CD300c by a novel monoclonal antibody induces the differentiation of monocytes to M1 macrophages","authors":"Su In Lee ,&nbsp;Haneul Kim ,&nbsp;Chang Ki Lim ,&nbsp;Jae Dong Kim ,&nbsp;Jeong Seok Heo ,&nbsp;Joongoo Jung ,&nbsp;Chan Kim ,&nbsp;Hong Jae Chon ,&nbsp;Jae-Won Jeon","doi":"10.1016/j.imbio.2023.152780","DOIUrl":"10.1016/j.imbio.2023.152780","url":null,"abstract":"<div><p>Human CD300c is expressed on various immune or cancer cells and is a novel B7 family member, functioning as an activity modulator on immune cells. To elucidate the function of CD300c, we developed CL7, a human CD300c-specific monoclonal antibody, and assessed its biological activity. The specific binding of CL7 monoclonal antibody against recombinant CD300c antigen was confirmed using enzyme-linked immunosorbent assay and surface plasmon resonance analysis. The binding affinity of CL7 was strong at the sub-nanomolar level. Furthermore, CL7 effectively bound to exogenously expressed CD300c on 293T cells. CL7 antibody differentiated monocytes to M1 macrophages, as evidenced by the upregulated expression of M1-specific cell surface markers and increased secretion of M1-specific cytokines in vitro in THP-1 cells and primary macrophages, as well as the increased population size of M1 macrophages in tumors grafted into mice. Additionally, CL7 treatment upregulated PD-L1 expression on THP-1 cells. We confirmed that the mechanism of M1 macrophage differentiation was through the mitogen-activated protein kinase and NF-κB signaling pathways. CD300c expression on various immune and cancer cells was similar to that of the well-known immune checkpoint PD-L1, suggesting the possibility of CD300c as a novel tumor biomarker. We also confirmed that the tumor size was substantially reduced by CL7 antibody treatment in the CT26 mouse model. Our study supports that CD300c is a potential therapeutic target in immuno-oncology. Overall, the CD300c-specific monoclonal antibody, CL7, is a promising immunotherapeutic agent, and it induces enhanced differentiation of M1 macrophages and/or their infiltration into the tumor microenvironment.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 1","pages":"Article 152780"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298523045825/pdfft?md5=375758e9582e44f7c9f0f15ee884fde0&pid=1-s2.0-S0171298523045825-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139024830","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":"Deletion of mesencephalic astrocyte-derived neurotrophic factor delays and damages the development of white pulp in spleen","authors":"Chengyue Zhou ,&nbsp;Dan Han ,&nbsp;Hui Fang ,&nbsp;Dake Huang ,&nbsp;Heping Cai ,&nbsp;Yujun Shen ,&nbsp;Yuxian Shen ,&nbsp;Jun Liu","doi":"10.1016/j.imbio.2023.152778","DOIUrl":"10.1016/j.imbio.2023.152778","url":null,"abstract":"<div><p>Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER) stress-induced protein, and it has been reported that ER stress and unfolded protein response (UPR) are closely related to the immune system. The spleen is an important immune organ and we have shown in our previous research that MANF is expressed in human spleen tissues. However, there have been limited studies about the effect of MANF on spleen development. In this study, we detected MANF expression in spleen tissues and found that MANF was expressed in the red pulp and marginal zone. Additionally, MANF was localized in the CD68⁺ and CD138⁺ cells of adult rat spleen tissues, but not in the CD3⁺ cells. We performed immunohistochemical staining to detect MANF expression in the spleen tissues of rats that were different ages, and we found that MANF⁺ cells were localized together in the spleen tissues of rats that were 1–4 weeks old. MANF was also expressed in CD68⁺ cells in the spleen tissues of rats and mice. Furthermore, we found that MANF deficiency inhibited white pulp development in MANF knockout mice, thus indicating that MANF played an important role in the white pulp development of rodent spleen tissues.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 1","pages":"Article 152778"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298523045801/pdfft?md5=e0df5365e5a9b2d2236b47d425aae6ab&pid=1-s2.0-S0171298523045801-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138987151","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":"Significance of m6A in subtype identification, immunological evolution, and therapeutic sensitivity of RA","authors":"Chenxi Ma ,&nbsp;Jiasheng Wu ,&nbsp;Hongwei Lei ,&nbsp;He Huang ,&nbsp;Yingnan Li","doi":"10.1016/j.imbio.2023.152781","DOIUrl":"10.1016/j.imbio.2023.152781","url":null,"abstract":"<div><p>N6-methyladenosine (m6A) is one kind of important epigenetic modification pattern which is extensively involved in immune regulation. The development and progression of autoimmune diseases are closely related to immune dysregulation. Considering that rheumatoid arthritis (RA) is a typical autoimmune disease, the m6A process might be one of the important regulatory mechanisms in the pathogenesis of RA. In this study, we identified five differentially expressed m6A regulators in normal and RA samples from the GEO database. With these five regulators, we constructed the nomogram, and it could accurately identify the risk of RA morbidity. Next, we identified 121 differentially expressed genes (DEGs) between normal and RA samples, of which 36 DEGs were co-expressed with these five m6A regulators. We noted that these DEGs were highly enriched in multiple immunoregulatory signaling pathways, such as cytokine-mediated immune cell chemotaxis, adhesion, and activation. To further characterize the heterogeneity of immunological features, we clustered the RA samples into two subtypes. The C2 subtype has higher infiltration levels of pro-inflammatory cells and activity of pro-inflammatory signaling pathways. Thus, the inflammatory response might be more vigorous in the C2 subtype. Next, we constructed the m6Asig system with the SVM machine learning algorithms and least absolute shrinkage and selection operator (LASSO) regression. The m6Asig could accurately distinguish the C1 and C2 subtypes, which indicated that the m6Asig could be a potential biomarker for the inflammatory activity of RA. Finally, by comparing the information from the CellMiner, TTD, and DrugBank databases, we determined 25 drugs. The targets of these drugs were positively correlated with m6Asig. To be clarified, the above findings were derived from bioinformatics and statistical analyses, and further experimental validation still requires. In summary, this study further revealed the m6A and immunoregulation mechanisms in RA pathogenesis. Also, the m6Asig could be a novel biomarker with potential applicability in the clinical management of RA.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 1","pages":"Article 152781"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298523045837/pdfft?md5=d760a30c22492641861650222d6e0b83&pid=1-s2.0-S0171298523045837-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139015122","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":"Toll-like receptor expression and functional behavior in platelets from patients with systemic lupus erythematosus","authors":"María C. Baroni Pietto ,&nbsp;Ana C. Glembotsky ,&nbsp;Paola R. Lev ,&nbsp;Cecilia R. Marín Oyarzún ,&nbsp;Geraldine De Luca ,&nbsp;Graciela Gomez ,&nbsp;María V. Collado ,&nbsp;Nancy Charó ,&nbsp;Adela S. Cellucci ,&nbsp;Paula G. Heller ,&nbsp;Nora P. Goette ,&nbsp;Rosana F. Marta","doi":"10.1016/j.imbio.2023.152782","DOIUrl":"10.1016/j.imbio.2023.152782","url":null,"abstract":"<div><h3>Background</h3><p>Multiple blood cell abnormalities participate in the development of inflammation in systemic lupus erythematosus (SLE). Although platelets have been suggested as one of these contributors through the release of their content during activation, there are limited specific data about their role as immune players in SLE.</p></div><div><h3>Materials and Methods</h3><p>Thirteen SLE patients were included. Flow cytometry was used to measure Toll-like receptors (TLR) 2, 4, and 9 in resting platelets, platelet-activation markers (PAC-1 binding, P-selectin, CD63, and CD40 ligand -L) and platelet-leukocyte aggregates before and after specific TLR stimulation. Soluble CD40L and von Willebrand factor (vWf) release from stimulated platelets was measured using ELISA.</p></div><div><h3>Results</h3><p>In resting conditions, SLE platelets showed normal expression levels of TLR 2, 4 and 9. Platelet surface activation markers, soluble CD40L, and vWf release were normal at baseline and after TLR stimulation. Platelet-monocyte aggregates were elevated in resting conditions in SLE samples and showed only a marginal increase after TLR stimulation, while baseline and stimulated platelet-neutrophil and platelet-lymphocyte aggregates were normal. C-reactive protein levels positively correlated with platelet-monocyte aggregates both at baseline and after stimulation with the TLR-2 agonist PAM3CSK4, suggesting these complexes could reflect the inflammatory activity in SLE. In our cohort, 12 of 13 patients received treatment with hydroxychloroquine (HCQ), a known inhibitor of endosomal activity and a potential inhibitor of platelet activation. The fact that SLE platelets showed an adequate response to TLR agonists suggests that, despite this treatment, they retain the ability to respond to the increased levels of damage-associated molecular patterns (DAMPs), which represent known TLR ligands, present in the circulation of SLE patients. Interestingly, elevated plasma levels of high mobility group box 1 (HMGB1), a classical DAMP, correlated with vWf release from TLR-stimulated platelets, suggesting that HMGB1 may also be released by platelets, thereby creating a positive feedback loop for platelet activation that contributes to inflammation.</p></div><div><h3>Conclusion</h3><p>Our study demonstrates normal platelet TLR expression and function together with increased circulating platelet-monocyte aggregates. In addition, a direct correlation was observed between plasma HMGB1 levels and platelet vWf release following TLR2 stimulation. This platelet behavior in a group of patients undergoing HCQ treatment suggests that platelets could play a role in the inflammatory state of SLE.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 1","pages":"Article 152782"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298523045849/pdfft?md5=428b046d1f34f9ef58d2ae3616a538fb&pid=1-s2.0-S0171298523045849-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139051626","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":"Significance of m6A in subtype identification, immunological evolution, and therapeutic sensitivity of RA","authors":"Chenxi Ma, Jiasheng Wu, Hongwei Lei, He Huang, Yingnan Li","doi":"10.1016/j.imbio.2023.152781","DOIUrl":"https://doi.org/10.1016/j.imbio.2023.152781","url":null,"abstract":"<p>N6-methyladenosine (m6A) is one kind of important epigenetic modification pattern which is extensively involved in immune regulation. The development and progression of autoimmune diseases are closely related to immune dysregulation. Considering that rheumatoid arthritis (RA) is a typical autoimmune disease, the m6A process might be one of the important regulatory mechanisms in the pathogenesis of RA. In this study, we identified five differentially expressed m6A regulators in normal and RA samples from the GEO database. With these five regulators, we constructed the nomogram, and it could accurately identify the risk of RA morbidity. Next, we identified 121 differentially expressed genes (DEGs) between normal and RA samples, of which 36 DEGs were co-expressed with these five m6A regulators. We noted that these DEGs were highly enriched in multiple immunoregulatory signaling pathways, such as cytokine-mediated immune cell chemotaxis, adhesion, and activation. To further characterize the heterogeneity of immunological features, we clustered the RA samples into two subtypes. The C2 subtype has higher infiltration levels of pro-inflammatory cells and activity of pro-inflammatory signaling pathways. Thus, the inflammatory response might be more vigorous in the C2 subtype. Next, we constructed the m6Asig system with the SVM machine learning algorithms and least absolute shrinkage and selection operator (LASSO) regression. The m6Asig could accurately distinguish the C1 and C2 subtypes, which indicated that the m6Asig could be a potential biomarker for the inflammatory activity of RA. Finally, by comparing the information from the CellMiner, TTD, and DrugBank databases, we determined 25 drugs. The targets of these drugs were positively correlated with m6Asig. To be clarified, the above findings were derived from bioinformatics and statistical analyses, and further experimental validation still requires. In summary, this study further revealed the m6A and immunoregulation mechanisms in RA pathogenesis. Also, the m6Asig could be a novel biomarker with potential applicability in the clinical management of RA.</p>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"11 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139028779","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":"ADAR1 regulates macrophage polarization and is protective against liver ischemia and reperfusion injury","authors":"Linxiao Wang ,&nbsp;Chujun Duan ,&nbsp;Xiuhua Wu ,&nbsp;Jiangang Xie ,&nbsp;Xiaojun Zhao ,&nbsp;Yi Si ,&nbsp;Dan Wu ,&nbsp;Yifan Wang ,&nbsp;Peng Zhao ,&nbsp;Jijun Chen ,&nbsp;Wen Yin ,&nbsp;Junjie Li","doi":"10.1016/j.imbio.2023.152777","DOIUrl":"10.1016/j.imbio.2023.152777","url":null,"abstract":"<div><p>Liver ischemia and reperfusion injury (LIRI) is a major risk for the poor prognosis of patients receiving liver transplantation. The molecular mechanism involved in LIRI is complex and related to various cellular components. We previously reported that adenosine deaminase acting on RNA 1 (ADAR1) alleviated the allogeneic skin graft rejection by regulating macrophage polarization. However, the regulatory effects of ADAR1 on liver macrophages after LIRI remain largely unknown. In this study, we mainly adopted a mouse model of LIRI and cellular experiments with hypoxia and reoxygenation (HR) treatment to explore the regulatory roles of ADAR1 on liver macrophages under LIRI conditions. We found that IRI caused decreased ADAR1 in liver tissues and remarkable changes of liver macrophage polarization and profiles. ADAR1 supplementation alleviated the pathological injury caused by IRI and accelerated the activation of M2 macrophages in the liver of IRI mice. Increased hypoxia duration reduced ADAR1 expression levels in murine RAW264.7 macrophages at the transcriptional level. Further overexpression of ADAR1 significantly increased the expressions of anti-inflammatory cytokines and promoted M2 polarization of macrophages under HR exposure. ADAR1 knockdown exhibited opposite effects on macrophage polarization. Hence, ADAR1 promotes the M2 polarization of liver macrophages that may further alleviate LIRI. The protective effects of ADAR1 against LIRI provide a novel insight into the prevention and treatment of LIRI.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 1","pages":"Article 152777"},"PeriodicalIF":2.8,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298523045795/pdfft?md5=a34f1199304f8318fb2dc83897551a8a&pid=1-s2.0-S0171298523045795-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138631730","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":"Chlorella vulgaris extract and Imiquimod as new therapeutic targets for leishmaniasis: An immunological approach","authors":"Maria Gabriella Nunes de Melo ,&nbsp;Isabelle Barreto da Silva Moreira Reino ,&nbsp;Victor Vaitkevicius-Antão ,&nbsp;Jady Moreira da Silva ,&nbsp;José Noé da Silva Júnior ,&nbsp;Alexsandra Frazão de Andrade ,&nbsp;Raquel Pedrosa Bezerra ,&nbsp;Daniela de Araújo Viana Marques ,&nbsp;Silvana de Fátima Ferreira da Silva ,&nbsp;Paulo Sérgio Ramos de Araújo ,&nbsp;Virginia Maria Barros de Lorena ,&nbsp;Rayana Carla Silva de Morais ,&nbsp;Milena de Paiva-Cavalcanti","doi":"10.1016/j.imbio.2023.152779","DOIUrl":"10.1016/j.imbio.2023.152779","url":null,"abstract":"<div><p>The therapeutic regimen for the treatment of American Tegumentary Leishmaniasis (ATL) is targeted at the death of the parasite; therefore, it is essential to develop a treatment that can act on the parasite, combined with the modulation of the inflammatory profile. Thus, the aim of this study was to make an <em>in vitro</em> evaluation of the therapeutic potential of <em>Chlorella vulgaris</em> extract (CV) and Imiquimod for ATL. Selectivity indices (SI) were determined by inhibitory concentration assays (IC₅₀) in <em>L</em>. <em>braziliensis</em> cells and cytotoxic concentrations (CC₅₀) were measured in human cells using the MTT method, based on the CV microalgae extract (IC₅₀ concentrations of 15.63 to 500 µg/mL; CC₅₀ concentrations of 62.5–1000 µg/mL) in comparison with the reference drugs and Imiquimod. The immune response was evaluated in healthy human cells by gene expression (RT-qPCR) and cytokine production (Flow Cytometry). The CV extract (SI = 6.89) indicated promising results by showing higher SI than meglumine antimoniate (SI = 3.44) (reference drug). In all analyses, CV presented a protective profile by stimulating the production of Th1 profile cytokines to a larger extent than the reference drugs. Imiquimod showed a high expression for Tbx21, GATA3, RORc and Foxp3 genes, with increased production only of the TNF cytokine. Therefore, the data highlight the natural extract and Imiquimod as strong therapeutic or adjuvant candidates against ATL, owing to modulation of immune response profiles, low toxicity in human cells and toxic action on the parasite.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 1","pages":"Article 152779"},"PeriodicalIF":2.8,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298523045813/pdfft?md5=1ba7d96e9ef7d01be83b646d18bd426f&pid=1-s2.0-S0171298523045813-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138631814","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":"Up-Regulation of scleral C5b-9 and Its regulation of the NLRP3 Inflammasome in a Form-Deprivation Myopia Mouse Model","authors":"Kang Xiao ,&nbsp;Zhengyu Chen ,&nbsp;Songqing He ,&nbsp;Qin Long","doi":"10.1016/j.imbio.2023.152776","DOIUrl":"10.1016/j.imbio.2023.152776","url":null,"abstract":"<div><h3>Background</h3><p>Myopia has become a major public health problem worldwide. Although the involvement of the complement system in myopia progression has been reported, the underlying mechanism has not been well established. In this study, we induced a form deprivation (FD) myopia mouse model to investigate the mechanisms.</p></div><div><h3>Methods</h3><p>Both C6-knockout (KO) and wild-type (WT) mice were divided into FD and normal control (NC) groups. The FD myopia was induced in the right eyes of 24-day-old mice using a translucent balloon for 4 weeks. The left eye remained untreated and served as self-control. NC group received no treatment. Refractive error and axial length were measured at baseline, 2 weeks, and 4 weeks later under normal visual, 4 weeks after FD. Scleral transcriptome sequencing analysis was performed in in FD mice. The scleral levels of C5b-9, NLRP3, Caspase-1, IL-1β, MMP-2, and collagen I were evaluated using immunohistochemistry.</p></div><div><h3>Results</h3><p>RNA-seq analysis showed 1058 differentially expressed genes. The GO analysis showed these genes were mainly related to the extracellular matrix, and immune response. The KEGG enrichment analysis showed that complement cascades were upregulated. Under normal visual conditions, both genotypes of mice exhibited comparable refractive error and axial length. However, after four weeks of FD, C6-KO mice showed a significantly less myopic shift (−2.28 ± 0.28 D versus −5.40 ± 1.33 D, <em>P</em> = 0.003), and axial shift (0.043 ± 0.032 mm versus 0.083 ± 0.026 mm, <em>P</em> = 0.042) in comparison to WT mice. Furthermore, the levels of C5b-9, NLRP3, caspase-1, IL-1β, and MMP-2 were found to be elevated in the deprived eyes of WT mice in comparison to their fellow eyes, whereas the extent of this increase was significantly lower in C6-KO mice.</p></div><div><h3>Conclusions</h3><p>Complement cascades are activated in FD myopia model. Upregulation of C5b-9 might participate in scleral remodeling during myopia progression via regulation of NLRP3 inflammasome activation.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 1","pages":"Article 152776"},"PeriodicalIF":2.8,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298523045783/pdfft?md5=1b7837a74a2206894e1eb8d04e3ba6b1&pid=1-s2.0-S0171298523045783-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138573254","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":"Vitexin along with verapamil downregulates efflux pump P-glycoprotein in macrophages and potentiate M1 to M2 switching via TLR4-NF-κB-TNFR2 pathway in lipopolysaccharide treated mice","authors":"Ayantika Kundu,&nbsp;Pratiti Ghosh ,&nbsp;Biswadev Bishayi","doi":"10.1016/j.imbio.2023.152767","DOIUrl":"10.1016/j.imbio.2023.152767","url":null,"abstract":"<div><p>The lipopolysaccharide, a microbial toxin, is one of the major causative agents of sepsis. P-gp expression and its functions are altered during inflammation. LPS has been known to impair the functions of P-gp, an efflux transporter. But the effect of LPS on P-gp expression in murine peritoneal macrophages is poorly understood. Molecular docking studies reveal that vitexin is a potent substrate and verapamil a potent inhibitor of P-gp. In the present experimental study, the curative potential of vitexin as a fruit component and verapamil treated as a control inhibitor of P-gp was examined in a murine LPS sepsis model. The effects of vitexin and verapamil on P-gp expression in macrophages correlating with changes in macrophage polarization and associated functional responses during LPS induced sepsis were studied. Peritoneal macrophages of LPS (10 mg/kg body weight) challenged mice exhibited elevated levels of H₂O₂, superoxide, and NO in parallel with lower antioxidant activity. LPS treatment increased P-gp expression through increased TLR4/expression. However, LPS challenged mice treated with vitexin (5 mg/kg body weight) + verapamil (5 mg/kg body weight) showed higher anti-oxidant enzyme activity (SOD, CAT and GRx) resulting in reduced oxidative stress. This combination treatment also elevated TNFR2, concomitant with down-regulation of TLR4, NF-κB and P-gp expression in murine peritoneal macrophages, resulting in a switch from M1 to M2 polarisation of macrophages and reduced inflammatory responses. In conclusion, combined vitexin and verapamil treatment could be used as a promising therapy to regulate P-gp expression and protection against LPS mediated sepsis and inflammatory damages.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 1","pages":"Article 152767"},"PeriodicalIF":2.8,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298523045692/pdfft?md5=f258a2275276a3345924fb357bc439d2&pid=1-s2.0-S0171298523045692-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138520274","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":"Alteration of PBMC transcriptome profile after interaction with multipotent mesenchymal stromal cells under “physiological” hypoxia","authors":"A.N. Gornostaeva ,&nbsp;P.I. Bobyleva ,&nbsp;E.R. Andreeva ,&nbsp;B.Sh. Gogiya ,&nbsp;L.B. Buravkova","doi":"10.1016/j.imbio.2023.152766","DOIUrl":"https://doi.org/10.1016/j.imbio.2023.152766","url":null,"abstract":"<div><p>Multipotent mesenchymal stromal cells (MSCs) have demonstrated a pronounced immunosuppressive activity, the manifestation of which depends on the microenvironmental factors, including O₂ level.</p><p>Here we examined the effects of MSCs on transcriptomic profile of allogeneic phytohemagglutinin-stimulated peripheral blood mononuclear cells (PBMCs) after interaction at ambient (20%) or “physiological” hypoxia (5%) O₂. As revealed with microarray analysis, PBMC transcriptome at 20% O₂ was more affected, which was manifested as differential expression of more than 300 genes, whereas under 5% O₂ 220 genes were changed. Most of genes at 20% O₂ were downregulated, while at hypoxia most of genes were upregulated. Altered gene patterns were only partly overlapped at different O₂ levels. A set of altered genes at hypoxia only was of particular interest. According to Gene Ontology a part of above genes was responsible for adhesion, cell communication, and immune response. At both oxygen concentrations, MSCs demonstrated effective immunosuppression manifested as attenuation of T cell activation and proliferation as well as anti-inflammatory shift of cytokine profile.</p><p>Thus, MSC-mediated immunosuppression is executed with greater efficacy at a “physiological” hypoxia, since the same result has been achieved through a change in the expression of a fewer genes in target PBMCs.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 1","pages":"Article 152766"},"PeriodicalIF":2.8,"publicationDate":"2023-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298523045680/pdfft?md5=4f8bae269ebf6ebbece4914aa4a559a4&pid=1-s2.0-S0171298523045680-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138570156","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}