Journal of Immunotoxicology最新文献

{"title":"Strategies to evaluate potential effector function of glycan variants: a case study of ordesekimab (AMG 714 or PRV-015).","authors":"Yu-Ling Wei,&nbsp;Teresa Wegesser,&nbsp;Scott Kuhns,&nbsp;Jonathan Werner,&nbsp;Hervé Lebrec,&nbsp;Xiaoting Wang","doi":"10.1080/1547691X.2022.2113841","DOIUrl":"https://doi.org/10.1080/1547691X.2022.2113841","url":null,"abstract":"<p><p>The potential for effector functions of therapeutic antibodies, including antibody-dependent cell-mediated cytotoxicity (ADCC), is a biological activity of interest for characterization, regardless of if ADCC is an intended primary pharmacological effect. The composition of the conserved antibody F_c glycan can vary as a function of post-translational processing which may affect the binding affinity to F_c receptors, leading to a change of effector activity. Ordesekimab (AMG 714 or PRV-015), a fully human immunoglobulin G₁-kappa anti-interleukin (IL)-15 monoclonal antibody, is in clinical development for celiac disease. The binding of ordesekimab to IL-15 inhibits the interaction of IL-15 with the IL-2Rβ and common γ chain of the IL-15 receptor complex, but not with the IL-15Rα chain. Therefore, the simultaneous binding of ordesekimab to the F_cγ receptor (R) IIIα expressed on natural killer (NK) cells and to the IL-15/IL-15Rα complex on cells such as monocytes may theoretically enable ADCC toward the IL-15Rα-expressing cells. The high mannose (HM) levels on the F_c glycan were found to vary in different lots of ordesekimab resulting from refinements to the manufacturing process, and the impact on ordesekimab-mediated ADCC activity was evaluated in <i>in vivo</i> and <i>in vitro</i> studies. A review of nonclinical and clinical data found no evidence of ordesekimab-induced depletion of monocytes, or cytotoxicity in organs with wide IL-15Rα expression, suggesting a lack of <i>in vivo</i> ADCC activity. In addition, <i>in vitro</i> peripheral blood mononuclear cells-based ADCC assay did not reveal any cytolytic effect of ordesekimab with various levels of HM content when cocultured with recombinant human IL-15. Taken together, these data demonstrate that ADCC is not a potential liability for ordesekimab and does not contribute to the reduction of IL-15-mediated inflammation, the intended pharmacological effect.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"19 1","pages":"109-116"},"PeriodicalIF":3.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10766329","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":"ROS-mediated inflammatory response in liver damage via regulating the Nrf2/HO-1/NLRP3 pathway in mice with trichloroethylene hypersensitivity syndrome.","authors":"Feng Wang,&nbsp;Yiting Hong,&nbsp;Wei Jiang,&nbsp;Yican Wang,&nbsp;Muyue Chen,&nbsp;Dandan Zang,&nbsp;Qixing Zhu","doi":"10.1080/1547691X.2022.2111003","DOIUrl":"https://doi.org/10.1080/1547691X.2022.2111003","url":null,"abstract":"<p><p>Trichloroethylene hypersensitivity syndrome (THS), mainly caused by occupational exposure to trichloroethylene (TCE), can give rise to serious and fatal hepatic damage. To date, the precise mechanisms of hepatic damage in THS remain unclear. Recent studies showed that reactive oxygen species (ROS) play a core role in cell death and inflammatory response. Therefore, the present study sought to explore whether ROS-mediated inflammatory responses contribute to the hepatic damage in TCE sensitization. To this end, a mouse model of TCE sensitization was established; in some cases, hosts were pretreated with tempol, an ROS scavenger. The results showed that TCE sensitization caused hepatic pathological/functional changes, ROS generation, and oxidative stress, alterations of the anti-oxidant defense Nrf2/HO-1/NLRP3 pathway, and pro-inflammatory cytokine formation in the liver. ROS scavenging via pretreatment with tempol was found not only to inhibit the hepatic oxidative stress, but also to regulate Nrf2/HO-1/NLRP3 pathway activity. In all cases, tempol was able to mitigate the pathologic changes induced by TCE sensitization. In summary, the results here demonstrated a novel molecular mechanism wherein ROS-mediated inflammatory responses play a central role in TCE-induced liver damage. Therapies targeting ROS scavenging could help to protect against hepatic damage by regulating Nrf2/HO-1/NLRP3 pathway activities in TCE-sensitized hosts.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"19 1","pages":"100-108"},"PeriodicalIF":3.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10417278","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":"Immunosafety evaluation in Juvenile Göttingen Minipigs.","authors":"Linda Allais,&nbsp;Alicia Perbet,&nbsp;Fabienne Condevaux,&nbsp;Jean-Paul Briffaux,&nbsp;Marc Pallardy","doi":"10.1080/1547691X.2022.2088904","DOIUrl":"https://doi.org/10.1080/1547691X.2022.2088904","url":null,"abstract":"<p><p>Although an extrapolation from the clinical experience in adults can often be considered to support the pediatric use for most pharmaceutical compounds, differences in safety profiles between adult and pediatric patients can be observed. The developing immune system may be affected due to exaggerated pharmacological or non-expected effects of a new drug. Toxicology studies in juvenile animals could therefore be required to better evaluate the safety profile of any new pharmaceutical compound targeting the pediatric population. The Göttingen minipig is now considered a useful non-rodent species for non-clinical safety testing of human pharmaceuticals. However, knowledge on the developing immune system in juvenile minipigs is still limited. The objective of the work reported here was to evaluate across-age proportions of main immune cells circulating in blood or residing in lymphoid organs (thymus, spleen, lymph nodes) in Göttingen Minipigs. In parallel, the main immune cell populations from healthy and immunocompromised piglets were compared following treatment with cyclosporin A (CsA) at 10 mg/kg/day for 4 wk until weaning. The study also assessed functionality of immune responses using an <i>in-vivo</i> model after \"Keyhole limpet hemocyanin\" (KLH) immunization and an <i>ex-vivo</i> lymph proliferation assay after stimulation with Concanavalin A. The results demonstrated variations across age in circulating immune cell populations including CD21⁺ B-cells, αβ-T- and γδ-T-cells, NK cells, and monocytes. CsA-induced changes in immune functions were only partially recovered by 5 mo after the end of treatment, whereas the immune cell populations affected by the treatment returned to normal levels in animals of the same age. Taken together, the study here shows that in this model, the immune function endpoints were more sensitive than the immunophenotyping endpoints.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"19 1","pages":"41-52"},"PeriodicalIF":3.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10420995","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":"Environmentally weathered polystyrene particles induce phenotypical and functional maturation of human monocyte-derived dendritic cells.","authors":"Annemijne E T van den Berg,&nbsp;Maud Plantinga,&nbsp;Dick Vethaak,&nbsp;Kas J Adriaans,&nbsp;Marianne Bol-Schoenmakers,&nbsp;Juliette Legler,&nbsp;Joost J Smit,&nbsp;Raymond H H Pieters","doi":"10.1080/1547691X.2022.2143968","DOIUrl":"https://doi.org/10.1080/1547691X.2022.2143968","url":null,"abstract":"<p><p>Micro- and nanoplastics (MNP) are ubiquitously present in the environment due to their high persistence and bioaccumulative properties. Humans get exposed to MNP via various routes and consequently, they will encounter dendritic cells (DC) which are antigen-presenting cells involved in regulating immune responses. The consequences of DC exposure to MNP are an important, yet understudied, cause of concern. Therefore, this study aimed to assess the uptake and effect of MNP <i>in vitro</i> by exposing human monocyte-derived dendritic cells (MoDC) to virgin and environmentally weathered polystyrene (PS) particles of different sizes (0.2, 1, and 10 µm), at different concentrations ranging from 1 to 100 µg/ml. The effects of these particles were examined by measuring co-stimulatory surface marker (i.e. CD83 and CD86) expression. In addition, T-cell proliferation was measured via a mixed-leukocyte reaction (MLR) assay. The results showed that MoDC were capable of absorbing PS particles, and this was facilitated by pre-incubation in heat-inactivated (HI) plasma. Furthermore, depending on their size, weathered PS particles in particular caused increased expression of CD83 and CD86 on MoDC. Lastly, weathered 0.2 µm PS particles were able to functionally activate MoDC, leading to an increase in T-cell activation. These <i>in vitro</i> data suggest that, depending on their size, weathered PS particles might act as an immunostimulating adjuvant, possibly leading to T-cell sensitization.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"19 1","pages":"125-133"},"PeriodicalIF":3.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10422921","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":"Dolutegravir potentiates platelet activation by a calcium-dependent, ionophore-like mechanism.","authors":"Morris Madzime,&nbsp;Annette J Theron,&nbsp;Ronald Anderson,&nbsp;Gregory R Tintinger,&nbsp;Helen C Steel,&nbsp;Pieter W A Meyer,&nbsp;Jan G Nel,&nbsp;Charles Feldman,&nbsp;Theresa M Rossouw","doi":"10.1080/1547691X.2022.2142705","DOIUrl":"https://doi.org/10.1080/1547691X.2022.2142705","url":null,"abstract":"<p><p>Dolutegravir is a highly potent HIV integrase strand transfer inhibitor that is recommended for first-line anti-retroviral treatment in all major treatment guidelines. A recent study has shown that people taking this class of anti-retroviral treatment have a substantially higher risk of early-onset cardiovascular disease, a condition shown previously to be associated with increased platelet reactivity. To date, few studies have explored the effects of dolutegravir on platelet activation. Accordingly, the current study was undertaken with the primary objective of investigating the effects of dolutegravir on the reactivity of human platelets <i>in vitro.</i> Platelet-rich plasma, isolated platelets, or buffy coat cell suspensions prepared from the blood of healthy adults were treated with dolutegravir (2.5-10 µg/ml), followed by activation with adenosine 5'-diphosphate (ADP), thrombin, or a thromboxane A₂ receptor agonist U46619. Expression of platelet CD62P (P-selectin), formation of heterotypic neutrophil:platelet aggregates, and calcium (Ca²⁺) fluxes were measured using flow cytometry and fluorescence spectrometry, respectively. Dolutegravir caused dose-related potentiation of ADP-, thrombin- and U46619-activated expression of CD62P by platelets, as well as a significant increases in formation of neutrophil:platelet aggregates. These effects were paralleled by a spontaneous, receptor-independent elevation in cytosolic Ca²⁺ that appears to underpin the mechanism by which the antiretroviral agent augments the responsiveness of these cells to ADP, thrombin and U46619. The most likely mechanism of dolutegravir-mediated increases in platelet cytosolic Ca²⁺ relates to a combination of lipophilicity and divalent/trivalent metal-binding and/or chelating properties of the anti-retroviral agent. These properties are likely to confer ionophore-type activities on dolutegravir that would promote movement of Ca²⁺ across the plasma membrane, delivering the cation to the cytosol where it would augment Ca²⁺-dependent intracellular signaling mechanisms. These effects of dolutegravir may lead to hyper-activation of platelets which, if operative <i>in vivo</i>, may contribute to an increased risk for cardiometabolic co-morbidities.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"19 1","pages":"1-8"},"PeriodicalIF":3.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10418527","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":"Expression and clinical significance of the m6A reader <i>YTHDF2</i> in peripheral blood mononuclear cells from rheumatoid arthritis patients.","authors":"Fangyi Yao,&nbsp;Chuxin Xu,&nbsp;Yujie Gao,&nbsp;Biqi Fu,&nbsp;Lu Zhang,&nbsp;Yang Guo,&nbsp;Zikun Huang,&nbsp;Xiaozhong Wang,&nbsp;Junming Li,&nbsp;Qing Luo","doi":"10.1080/1547691X.2022.2067916","DOIUrl":"https://doi.org/10.1080/1547691X.2022.2067916","url":null,"abstract":"Abstract As an important m6A reader, the YT521-B homology domain family 2 (YTHDF2) has been shown to regulate mRNA degradation and translation, and to be involved in inflammation. However, little is known about the role of YTHDF2 in the autoimmune-based inflammatory disease rheumatoid arthritis (RA). To begin to ascertain any role for this reader, 74 RA patients and 63 healthy controls (HC) were recruited for this study. Blood was collected from each subject and peripheral blood mononuclear cells (PBMC) isolated. Thereafter, mRNA expression of YTHDF2, interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α in the cells was determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The harvested blood was also assessed for a variety of parameters, including levels of C-reactive protein (CRP), erythrocyte sedimentation rates (ESR), white blood cell counts (WBC), neutrophils counts (N)/neutrophils percentages (N%), and neutrophil:lymphocyte ratios (NLR) - each markers of inflammation during RA. The results showed that YTHDF2 mRNA expression in RA patient PBMC was decreased significantly vs that in healthy control subject cells. Further, YTHDF2 mRNA expression in RA patient PBMC negatively-correlated with ESR, CRP levels, WBC counts, as well as neutrophils counts, percentages, and NLR values. In addition, it was seen that YTHDF2 mRNA expression in RA patient PBMC was associated with host serum RF levels and treatment. Moreover, it was found that mRNA expression of IL-1β, IL-6, IL-8, and TNFα was increased in PBMC from RA patients relative to in control subject cells; however, only the increased IL-1β expression was seen to be negatively-correlated with decreased YTHDF2 mRNA expression. In conclusion, the present study illustrated that YTHDF2 expression might have some regulatory role in the underlying mechanisms associated with the autoimmune disease RA and that this m6A reader could at some point represent a potential target for regulating inflammatory responses that occur during RA.","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"19 1","pages":"53-60"},"PeriodicalIF":3.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10408016","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":"Bisphenol A, T_H17 cells, and allergy: a commentary.","authors":"Ian Kimber,&nbsp;Nicole Woeffen,&nbsp;Kevin Sondenheimer","doi":"10.1080/1547691X.2022.2113842","DOIUrl":"https://doi.org/10.1080/1547691X.2022.2113842","url":null,"abstract":"<p><p>There is a continuing interest in whether Bisphenol A (BPA) is able to cause adverse health effects through interaction with elements of the immune system. That interest has been fuelled further by the recent publication of a draft opinion on BPA prepared by the European Food Safety Authority (EFSA) Panel on Food Contact Materials, Enzymes and Processing Aids (CEP). This draft opinion judged effects on the immune system to be the most sensitive health outcome, and identified BPA-induced changes in the frequency of T-helper (T_H)-17 cells in the spleens of mice as being the critical effect based on an association of these cells with inflammation. Based on these evaluations the CEP Panel recommended that a revised Tolerable Daily Intake (TDI) for BPA of 0.04 ng/kg bw/day should be adopted; representing a very substantial reduction (100,000-fold) compared with the existing TDI. The purpose of this commentary is to summarize briefly the role of T_H17 cells in immune responses, and to review relevant literature regarding the influence of BPA on these cells, and on inflammatory responses in the lung and respiratory allergy. The conclusion drawn is that based on uncertainties about the effects of BPA on T_H17 cells and lung inflammation in mice, the absence of consistent or persuasive evidence from human studies that exposure of BPA is associated with inflammation or allergy, and unresolved questions regarding the species selectivity of immune effects induced by BPA, it is inappropriate to adopt the revised TDI. Additional research is required to explore further the influence of BPA on the immune system and immune responses.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"19 1","pages":"93-99"},"PeriodicalIF":3.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10417275","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":"A T-cell-dependent antibody response (TDAR) method in BALB/c mice based on a cytometric bead array","authors":"Wenhua Zhong, Penghuan Chang, Lianfang Gan, Lifan Zhong, Zhaoxin Yang","doi":"10.1080/1547691X.2022.2067273","DOIUrl":"https://doi.org/10.1080/1547691X.2022.2067273","url":null,"abstract":"Abstract Most current methods to assess T-cell-dependent antibody responses (TDAR) are semi-quantitative and based on measures of antibody titer generated against a standard antigen like keyhole limpet hemocyanin (KLH). The precision, sensitivity, and convenience of TDAR assays might be improved by applying rapid, sensitive, specific cytometric bead assays (CBA). In the study here, KLH antigen was covalently coupled onto the surface of cytometric beads using immune microsphere technology, and IgM antibody capture spheres were prepared for use in pretreatment processing of samples. The working parameters associated with this novel TDAR-CBA system were optimized in orthogonal experiments. The optimal concentration of the KLH coating solution in this system was 160 μg/ml, that of the anti-KLH IgG capture spheres 6.0 × 105/ml, and the optimal dilution of fluorescein isothiocyanate (FITC)-conjugated Affini-Pure Goat Anti-Mouse IgG (H + L) was 60 μg/ml. Repeated tests indicated that this approach yielded good linearity (r 2 = 0.9937) method, with a within-run precision of 3.1–4.9%, and a between-run precision of 4.4–4.9%. This new approach had a limit of detection of 113.43 ng/ml (linear range = 390.63–50 000), and an interference rate of just 0.04–3.51%. Based on these findings, it seems that a new mouse TDAR assay based on CBA can be developed that would appear to be more sensitive, accurate, and precise than the current TDAR assay approaches based on traditional ELISA.","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"19 1","pages":"34 - 40"},"PeriodicalIF":3.3,"publicationDate":"2022-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43203050","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":"Proteolytic activity accelerates the TH17/TH22 recall response to an epicutaneous protein allergen-induced TH2 response","authors":"A. Ogasawara, T. Yuki, Asuka Katagiri, Yi-Ting Lai, Yutaka Takahashi, D. Basketter, H. Sakaguchi","doi":"10.1080/1547691X.2022.2049665","DOIUrl":"https://doi.org/10.1080/1547691X.2022.2049665","url":null,"abstract":"Abstract Epicutaneous exposure to protein allergens, such as papain, house dust mite (HDM), and ovalbumin (OVA), represents an important mode of sensitization for skin diseases including protein contact dermatitis, immunologic contact urticaria, and atopic dermatitis. These diseases are inducible by re-exposure to an allergen at both original skin sensitization and distant skin sites. In this study, we examined the serum IgE/IgG1 response, differentiation of T-helper (TH) cells, and epicutaneous TH recall response in mice pre-sensitized with protein allergens through the back skin and subsequently challenged on the ear skin. Repeated epicutaneous sensitization with allergenic proteins including papain, HDM, OVA, and protease inhibitor-treated papain, but not bovine serum albumin, induced serum allergen-specific antibody production, passive cutaneous anaphylaxis responses, and TH2 differentiation in the skin draining lymph node (DLN) cells. Sensitization with papain or HDM, which have protease activity, resulted in the differentiation of TH17 as well as TH2. In papain- or HDM-sensitized mice, a subsequent single challenge on the ear skin induced the expression of TH2 and TH17/TH22 cytokines. These results suggest that allergenic proteins induce the differentiation of TH2 in skin DLN cells and an antibody response. These findings may be useful for identifying proteins of high and low allergenic potential. Moreover, allergenic proteins containing protease activity may also differentiate TH17 and induce TH2 and TH17/TH22 recall responses at epicutaneous challenge sites. This suggests that allergen protease activity accelerates the onset of skin diseases caused by protein allergens.","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"19 1","pages":"27 - 33"},"PeriodicalIF":3.3,"publicationDate":"2022-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43805967","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":"Gallic acid attenuates cerebral ischemia/re-perfusion-induced blood–brain barrier injury by modifying polarization of microglia","authors":"Yang Qu, Lin Wang, Yanfang Mao","doi":"10.1080/1547691X.2022.2043494","DOIUrl":"https://doi.org/10.1080/1547691X.2022.2043494","url":null,"abstract":"Abstract Microglia, the main immune effector cells in the central nervous system, play a dual role in the function/structure of the blood–brain barrier (BBB) and brain health. During and soon after a cerebral ischemic injury, microglia produce neurotrophic factors and neurotoxins that can impact on the injury itself and pathology progression. At the same time, microglia undergo polarization to M1 or M2 pro- vs. anti-inflammatory subtypes that also help drive the outcome of the injury process. Thus, agents that can mitigate cerebral ischemic injury progression, promote protective functions of microglia, and help maintain BBB and overall brain health/host neurologic function after a cerebral ischemic event would be of great use in clinical settings. Protective effects from gallic acid (GA) in cerebral ischemia/re-perfusion-induced injury to the BBB and other sites in the brain have not yet been assessed. To address this, a middle cerebral artery occlusion (MCAO) method was used to establish an experimental ischemic stroke model in mice. Mice were placed in sham operation (Sham), model (MCAO), MCAO + GA (50 mg/kg), MCAO + GA (100 mg/kg), or MCAO + GA (150 mg/kg) groups. At various times post-stroke, cerebral infarct volume and host neurological function were evaluated. In addition, qRT-PCR, Western blotting, and ELISA were used to evaluate the expression and tissue content of microglia-related factors. The results showed GA treatment protected the integrity of the BBB, significantly reduced brain edema, and helped lead to improved neurological function scores in the MCAO mice. Whether these changes were due to that GA attenuated cerebral ischemia/re-perfusion-induced activation of microglial cells overall, in part, by inhibiting their polarization to the M1 subtype, is uncertain. Taking these outcomes together, for now it is reasonable to suggest that use of GA either as a prophylactic or immediately in the event of a cerebral ischemic event/stroke could help to promote neuronal survival and allow for a more likely of host neurological function over time.","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"19 1","pages":"17 - 26"},"PeriodicalIF":3.3,"publicationDate":"2022-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"59983522","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}