Journal of Immunotoxicology最新文献

{"title":"Divergent hypersensitivity responses following topical application of the quaternary ammonium compound, didecyldimethylammonium bromide.","authors":"Hillary L Shane,&nbsp;Ewa Lukomska,&nbsp;Aleksandr B Stefaniak,&nbsp;Stacey E Anderson","doi":"10.1080/1547691X.2017.1397826","DOIUrl":"https://doi.org/10.1080/1547691X.2017.1397826","url":null,"abstract":"<p><p>Didecyldimethylammonium bromide (DDAB) is a fourth generation dialkyl-quaternary ammonium compound (QAC) that is used in numerous products for its antimicrobial properties. While many QACs have been associated with allergic disease, the toxicity and sensitization of DDAB have not been thoroughly investigated. The purpose of these studies was to evaluate the irritancy and sensitization potential of DDAB following dermal application in a murine model. DDAB induced significant irritancy (0.0625-2%), evaluated by ear swelling in female BALB/c mice. Initial evaluation of the sensitization potential was conducted using the local lymph node assay (LLNA) at concentrations ranging from 0.0625% to 2%. A concentration-dependent increase in lymphocyte proliferation was observed with a calculated EC3 value of 0.057%. Immune cell phenotyping along with local and systemic IgE levels were evaluated following 4 and 14 days of dermal application. Phenotypic analyses revealed significant and dose-responsive increases in the absolute number of B-cells, CD4⁺ T-cells, CD8⁺ T-cells, and dendritic cells in the draining lymph nodes (DLNs) following 4 and 14 days of dermal exposure with significant increases in the number of activated B-cells and dendritic cells. However, increased activation of CD4⁺ T-cell and CD8⁺ T-cells was only observed following four days of DDAB exposure. Exposure to DDAB also induced increased production of IgE as evaluated by phenotypic analysis of DLN B-cells (IgE⁺ B-cells) and measurement of total serum IgE levels following 14 days but not four days of dermal application. Significant increases in gene expression were observed in the DLN (Il-4, Il-10, and ox40l) and ear (tslp) following 4 and 14 days of DDAB exposure. These results demonstrate the potential for development of irritation and hypersensitivity responses to DDAB following dermal exposure and raise concerns about the effects of exposure duration on hypersensitivity responses.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"14 1","pages":"204-214"},"PeriodicalIF":3.3,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/1547691X.2017.1397826","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35244441","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":"Assessment of immunotoxicity in female Fischer 344/N and Sprague Dawley rats and female B₆C₃F₁ mice exposed to hexavalent chromium via the drinking water.","authors":"Kelly A Shipkowski,&nbsp;Christopher M Sheth,&nbsp;Matthew J Smith,&nbsp;Michelle J Hooth,&nbsp;Kimber L White,&nbsp;Dori R Germolec","doi":"10.1080/1547691X.2017.1394932","DOIUrl":"https://doi.org/10.1080/1547691X.2017.1394932","url":null,"abstract":"<p><p>Sodium dichromate dihydrate (SDD), an inorganic compound containing hexavalent chromium (Cr(VI)), is a common environmental contaminant of groundwater sources due to widespread industrial use. There are indications in the literature that Cr(VI) may induce immunotoxic effects following dermal exposure, including acting as both an irritant and a sensitizer; however, the potential immunomodulatory effects of Cr(VI) following oral exposure are relatively unknown. Following the detection of Cr(VI) in drinking water sources, the National Toxicology Program (NTP) conducted extensive evaluations of the toxicity and carcinogenicity of SDD following drinking water exposure, including studies to assess the potential for Cr(VI) to modulate immune function. For the immunotoxicity assessments, female Fischer 344/N (F344/N) and Sprague Dawley (SD) rats and female B₆C₃F₁ mice were exposed to SDD in drinking water for 28 consecutive days and evaluated for alterations in cellular and humoral immune function as well as innate immunity. Rats were exposed to concentrations of 0, 14.3, 57.3, 172, or 516 ppm SDD while mice were exposed to concentrations of 0, 15.6, 31.3, 62.5, 125, or 250 ppm SDD. Final mean body weight and body weight gain were decreased relative to controls in 250 ppm B₆C₃F₁ mice and 516 ppm SD rats. Water consumption was significantly decreased in F344/N and SD rats exposed to 172 and 516 ppm SDD; this was attributed to poor palatability of the SDD drinking water solutions. Several red blood cell-specific parameters were significantly (5-7%) decreased in 250 ppm mice; however, these parameters were unaffected in rats. Sporadic increases in the spleen IgM antibody response to sheep red blood cells (SRBC) were observed, however, these increases were not dose-dependent and were not reproducible. No significant effects were observed in the other immunological parameters evaluated. Overall, exposure to Cr(VI) in drinking water had limited effects on the immune system in both rats and mice.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"14 1","pages":"215-227"},"PeriodicalIF":3.3,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/1547691X.2017.1394932","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35252160","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":"Long form of thymic stromal lymphopoietin of keratinocytes is induced by protein allergens.","authors":"Yasutaka Kuroda,&nbsp;Takuo Yuki,&nbsp;Yutaka Takahashi,&nbsp;Hitoshi Sakaguchi,&nbsp;Kayoko Matsunaga,&nbsp;Hiroshi Itagaki","doi":"10.1080/1547691X.2017.1349220","DOIUrl":"https://doi.org/10.1080/1547691X.2017.1349220","url":null,"abstract":"<p><p>A growing body of evidence suggests that epicutaneous sensitization of protein allergens induces immediate-type hypersensitivity (IHS) following induction of Type 2 immune responses in animals and humans. Thymic stromal lymphopoietin (TSLP) derived from keratinocytes is a cytokine that can activate dendritic cells and has been implicated in development of inflammatory Type 2 helper T-cells. However, there is no direct evidence that allergens directly regulate TSLP expression in keratinocytes. This study aimed to evaluate the response of TSLP to protein allergens in cultured human keratinocytes and to identify appropriate endpoints for IHS. The transcription of long-form TSLP (loTSLP) was strongly induced by ovalbumin, wheat gluten (WG), acid-hydrolyzed WG (acid-HWG), and extracts from feces of Dermatophagoides pteronyssinus and D. farina, and trypsin, but not by rare allergens, human serum albumin (HSA), or extracts of mite bodies. In acid-HWG, loTSLP mRNA was significantly augmented by acid hydrolysis of WG for 0.5 h compared to WG. However, prolonged acid hydrolysis attenuated this induction similarly to that reported in previous animal studies. These results suggested that intense loTSLP transcriptional induction was a characteristic of a high-allergenic protein. Additionally, TSLP production was induced by exposure to ovalbumin, WG, and acid-HWG in combination with a trio of cytokines, i.e. interleukin (IL)-4, IL-13, and tumor necrosis factor (TNF)-α. However, no TSLP protein was detected following exposure to HSA, even in the presence of these cytokines. With acid-HWG, TSLP protein release was consistent with loTSLP transcription. Thus, intense loTSLP transcriptional induction and TSLP protein expression are each effective indicators that can be used for in vitro screening of IHS.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"14 1","pages":"178-187"},"PeriodicalIF":3.3,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/1547691X.2017.1349220","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35178705","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":"Anti-drug antibodies in Colombian patients with rheumatoid arthritis treated with Enbrel vs Etanar - Preliminary report.","authors":"Benjamín Reyes-Beltrán,&nbsp;Gabriela Delgado","doi":"10.1080/1547691X.2017.1317885","DOIUrl":"https://doi.org/10.1080/1547691X.2017.1317885","url":null,"abstract":"<p><p>The present study was undertaken to detect antibodies against etanercept (ETN) in a group of Colombian patients with rheumatoid arthritis (RA) and being treated with Enbrel^® vs. Etanar^®. From these patients with RA, clinical and laboratory data were collected and serum taken for anti-drug antibody (ADAb) analysis. Samples from 32 patients (16 who had been treated with Enbrel^® and 16 with Etanar^®) were analyzed. Positive sera for ADAb were found in six of the 32 subjects (18.7%); five (31.2%) in the Enbrel^® group and one (6.25%) in the Etanar^® group. Patients under treatment with Enbrel^® registered a longer disease duration than patients being treated with Etanar^® (15.4 years vs. 10.98 years, p = 0.175) as well as a longer average treatment with the drug (45.7 vs. 23.9 months, p = 0.052). The percentage of patients with disease activity defined as a disease activity score by C-reactive protein (DAS28-CRP) scores ≥2.3 was higher in those patients with positive sera in the enzyme-linked immunosorbent assay (ELISA) (66.7%) than in those with negative sera (34.6%). A logistic regression test revealed that the higher the DAS28-CRP value, the higher the ELISA absorbance value. The results showed evidence of greater frequency of ADAb in patients treated with ETN than has been reported to date. Greater disease activity was seen in those patients in whose serum ADAb had been detected. Significant differences were found between the positive ELISA for the group of patients treated with Enbrel^® compared to those treated with Etanar^®. Some of the factors that could explain this difference are the length of the treatment time with the drug, the commercial ELISA kit used to detect ADAb, or the immunogenicity itself of each product.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"14 1","pages":"103-108"},"PeriodicalIF":3.3,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/1547691X.2017.1317885","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34932243","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 single dose of trichloroethylene given during development does not substantially alter markers of neuroinflammation in brains of adult mice.","authors":"Jacqueline R Meadows,&nbsp;Chevonne Parker,&nbsp;Kathleen M Gilbert,&nbsp;Sarah J Blossom,&nbsp;Jamie C DeWitt","doi":"10.1080/1547691X.2017.1305021","DOIUrl":"https://doi.org/10.1080/1547691X.2017.1305021","url":null,"abstract":"<p><p>Trichloroethylene (TCE) is a widespread environmental contaminant associated with developmental immunotoxicity and neurotoxicity. Previous studies have shown that MRL^+/+ mice exposed to TCE from gestation through early-life demonstrate robust increases in inflammatory markers in peripheral CD4⁺ T-cells, as well as glutathione depletion and increased oxidative stress in cerebellum-associated with alterations in behavior. Since increased oxidative stress is associated with neuroinflammation, we hypothesized that neuroinflammatory markers could be altered relative to unexposed mice. MRL^+/+ mice were given 0.5 mg/ml of TCE in vehicle or vehicle (water with 1% Alkamuls EL-620) from conception through early adulthood via drinking water to dams and then directly to post-weaning offspring. Animals were euthanized at 49 days of age and levels of pro- and anti-inflammatory cytokines, density of T-cell staining, and micro-glial morphology were evaluated in brains to begin to ascertain a neuroinflammatory profile. Levels of IL-6 were decreased in female animals and while not statistically significant, and levels of IL-10 were higher in brains of exposed male and female animals. Supportive of this observation, although not statistically significant, the number of ameboid microglia was higher in exposed relative to unexposed animals. This overall profile suggests the emergence of an anti-inflammatory/neuroprotective phenotype in exposed animals, possibly as a compensatory response to neuroinflammation that is known to be induced by developmental exposure to TCE.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"14 1","pages":"95-102"},"PeriodicalIF":3.3,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/1547691X.2017.1305021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34875826","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":"Impact of exposure time, particle size and uptake pathway on silver nanoparticle effects on circulating immune cells in mytilus galloprovincialis.","authors":"Younes Bouallegui,&nbsp;Ridha Ben Younes,&nbsp;Faten Turki,&nbsp;Ridha Oueslati","doi":"10.1080/1547691X.2017.1335810","DOIUrl":"https://doi.org/10.1080/1547691X.2017.1335810","url":null,"abstract":"<p><p>Nanomaterials have increasingly emerged as potential pollutants to aquatic organisms. Nanomaterials are known to be taken up by hemocytes of marine invertebrates including Mytilus galloprovincialis. Indeed, assessments of hemocyte-related parameters are a valuable tool in the determination of potentials for nanoparticle (NP) toxicity. The present study assessed the effects from two size types of silver nanoparticles (AgNP: <50 nm and <100 nm) on the frequency of hemocytes subpopulations as immunomodulation biomarkers exposed in a mollusk host. Studies were performed using exposures prior to and after inhibition of potential NP uptake pathways (i.e. clathrin- and caveolae-mediated endocytosis) and over different durations of exposure (3, 6 and 12 h). Differential hemocyte counts (DHC) revealed significant variations in frequency of different immune cells in mussels exposed for 3 hr to either AgNP size. However, as exposure duration progressed cell levels were subsequently differentially altered depending on particle size (i.e. no significant effects after 3 h with larger AgNP). AgNP effects were also delayed/varied after blockade of either clathrin- or caveolae-mediated endocytosis. The results also noted significant negative correlations between changes in levels hyalinocytes and acidophils or in levels basophils and acidophils as a result of AgNP exposure. From these results, we concluded AgNP effects on mussels were size and duration of exposure dependent. This study highlighted how not only was NP size important, but that differing internalization mechanisms could be key factors impacting on the potential for NP in the environment to induce immunomodulation in a model/test sentinel host like M. galloprovincialis.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"14 1","pages":"116-124"},"PeriodicalIF":3.3,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/1547691X.2017.1335810","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35081641","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":"Estimated exposures to perfluorinated compounds in infancy predict attenuated vaccine antibody concentrations at age 5-years.","authors":"Philippe Grandjean,&nbsp;Carsten Heilmann,&nbsp;Pal Weihe,&nbsp;Flemming Nielsen,&nbsp;Ulla B Mogensen,&nbsp;Amalie Timmermann,&nbsp;Esben Budtz-Jørgensen","doi":"10.1080/1547691X.2017.1360968","DOIUrl":"https://doi.org/10.1080/1547691X.2017.1360968","url":null,"abstract":"<p><p>Perfluorinated alkylate substances (PFASs) are highly persistent and may cause immunotoxic effects. PFAS-associated attenuated antibody responses to childhood vaccines may be affected by PFAS exposures during infancy, where breastfeeding adds to PFAS exposures. Of 490 members of a Faroese birth cohort, 275 and 349 participated in clinical examinations and provided blood samples at ages 18 months and 5 years. PFAS concentrations were measured at birth and at the clinical examinations. Using information on duration of breastfeeding, serum-PFAS concentration profiles during infancy were estimated. As outcomes, serum concentrations of antibodies against tetanus and diphtheria vaccines were determined at age 5. Data from a previous cohort born eight years earlier were available for pooled analyses. Pre-natal exposure showed inverse associations with the antibody concentrations five years later, with decreases by up to about 20% for each two-fold higher exposure, while associations for serum concentrations at ages 18 months and 5 years were weaker. Modeling of serum-PFAS concentration showed levels for age 18 months that were similar to those measured. Concentrations estimated for ages 3 and 6 months showed the strongest inverse associations with antibody concentrations at age 5 years, particularly for tetanus. Joint analyses showed statistically significant decreases in tetanus antibody concentrations by 19-29% at age 5 for each doubling of the PFAS exposure in early infancy. These findings support the notion that the developing adaptive immune system is particularly vulnerable to immunotoxicity during infancy. This vulnerability appears to be the greatest during the first 6 months after birth, where PFAS exposures are affected by breast-feeding.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"14 1","pages":"188-195"},"PeriodicalIF":3.3,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/1547691X.2017.1360968","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35409969","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":"Early immunopathological events in acute model of mycobacterial hypersensitivity pneumonitis in mice","authors":"E. Johansson, G. Boivin, J. Yadav","doi":"10.1080/1547691X.2016.1273284","DOIUrl":"https://doi.org/10.1080/1547691X.2016.1273284","url":null,"abstract":"Abstract Prolonged exposure to antigens of non-tuberculous mycobacteria species colonizing industrial metalworking fluid (MWF), particularly Mycobacterium immunogenum (MI), has been implicated in chronic forms of hypersensitivity pneumonitis (HP) in machinists based on epidemiology studies and long-term exposure of mouse models. However, a role of short-term acute exposure to these antigens has not been described in the context of acute forms of HP. This study investigated short-term acute exposure of mice to MI cell lysate (or live cell suspension) via oropharyngeal aspiration. The results showed there was a dose- and time-dependent increase (peaking at 2 h post-instillation) in lung immunological responses in terms of the pro- (TNFα, IL-6, IL-1β) and anti-inflammatory (IL-10) cytokines. Bronchoalveolar lavage and histology showed neutrophils as the predominant infiltrating cell type, with lymphocytes <5% at all timepoints or concentrations. Granulomatous inflammation peaked between 8 and 24 h post-exposure, and resolved by 96 h. Live bacterial challenge, typically encountered in real-world exposures, showed no significant differences from bacterial lysate except for induction of appreciable levels of interferon (IFN)-γ, implying additional immunogenic potential. Collectively, the short-term mycobacterial challenge in mice led to a transient early immunopathologic response, with little adaptive immunity, which is consistent with events associated with human acute forms of HP. Screening of MWF-originated mycobacterial genotypes/variants (six of MI, four of M. chelonae, two of M. abscessus) showed both inter- and intra-species differences, with MI genotype MJY10 being the most immunogenic. In conclusion, this study characterized the first short-term mycobacterial exposure mouse model that mimics acute HP in machinists; this could serve as a potentially useful model for rapid screening of field MWF-associated mycobacteria for routine and timely occupational risk assessment and for investigating early biomarkers and mechanisms of this understudied immune lung disease.","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"14 1","pages":"77 - 88"},"PeriodicalIF":3.3,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/1547691X.2016.1273284","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45353290","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":"Protective role of bentonite against aflatoxin B1- and ochratoxin A-induced immunotoxicity in broilers","authors":"S. Bhatti, M. Z. Khan, M. Saleemi, M. Saqib, Ahrar Khan, Z. Ul-Hassan","doi":"10.1080/1547691X.2016.1264503","DOIUrl":"https://doi.org/10.1080/1547691X.2016.1264503","url":null,"abstract":"Abstract The present study was designed to investigate any ameliorative effects of bentonite (BN) against immuno-pathological alterations induced by dietary aflatoxin B1 (AFB1) or ochratoxin A (OTA) in broiler chicks. In one experiment, AFB1 (0.1, 0.2 or 0.6 mg/kg feed) was fed alone and par alley with bentonite clay (3.7 or 7.5 g/kg feed) to the broilers. In the second experiment, the broilers were given feed contaminated with OTA (0.15, 0.3 or 1.0 mg/kg feed) alone and in combination with bentonite clay (3.7, 7.5, or 15 g/kg feed). Experimental feedings were continued for 42 days. At various time points along the feeding schedule, immune system organ histologic status, as well as host humoral and cellular immune responses, were evaluated in all groups. The dietary addition of AFB1 and OTA alone significantly reduced immune responses in the birds as assessed by histological changes in the bursa of Fabricius and thymus, antibody responses to SRBC, in-vivo lympho-proliferative responses to Phytohemagglutinin-P (PHA-P) and, phagocytic function in situ. The dietary addition of BN significantly ameliorated the immunotoxicity of 0.1 and 0.2 mg/kg dietary AFB1, however with a level of 0.6 mg AFB1/kg only partial amelioration was seen. The co-treatment of birds exposed to OTA with BN at all levels only partially alleviated deleterious effects on histology and immune responses. Taken together, the results here suggested to us that dietary addition of BN could help ameliorate AFB1-mediated immunotoxicities but could not afford such protection against OTA-induced immune damage.","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"14 1","pages":"66 - 76"},"PeriodicalIF":3.3,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/1547691X.2016.1264503","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49066934","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":"Effects of fostriecin on β2-adrenoceptor-driven responses in human mast cells","authors":"R. Bastan, N. Eskandari, Hamidrez J Ardakani, Peter T Peachell","doi":"10.1080/1547691X.2016.1259277","DOIUrl":"https://doi.org/10.1080/1547691X.2016.1259277","url":null,"abstract":"Abstract As part of the intracellular processes leading to mast cell and basophil activation, phosphorylation of key substrates is likely to be important. These processes, mediated by phosphatases, are responsible for regulating phosphorylation. The aim of the present study was to determine effects fostriecin – a selective inhibitor of PP2A (protein phosphatase-2) – on β2-adrenoceptor-driven responses in human mast cells. Here, the effects of fostriecin (PP inhibitors) on the inhibition of histamine release from HLMC, on β-adrenoceptor-driven responses in mast cells and on desensitization were investigated. Long-term incubation (24 h) of mast cells with fostriecin (10−6 M) resulted in a significant (p < 0.001) reduction in the maximal response (from 41.2 [± 3.0] to 29.9 [± 4.2] %) to salbutamol following fostriecin treatment. The results showed that fostriecin pretreatment significantly attenuated the inhibitory effects of salbutamol. Overall, the present study suggested that PP2A has an important role in regulating mast cell β2-adrenoceptors.","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"14 1","pages":"60 - 65"},"PeriodicalIF":3.3,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/1547691X.2016.1259277","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45442491","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}