Journal of Immunotoxicology最新文献

{"title":"Genetics and immunodysfunction underlying Behçet's disease and immunomodulant treatment approaches.","authors":"Arash Salmaninejad,&nbsp;Arezoo Gowhari,&nbsp;Seyedmojtaba Hosseini,&nbsp;Saeed Aslani,&nbsp;Meysam Yousefi,&nbsp;Tayyeb Bahrami,&nbsp;Masoume Ebrahimi,&nbsp;Abolfazl Nesaei,&nbsp;Masoud Zal","doi":"10.1080/1547691X.2017.1346008","DOIUrl":"https://doi.org/10.1080/1547691X.2017.1346008","url":null,"abstract":"<p><p>Behçet's disease (BD) is a chronic autoimmune condition primarily prevalent in populations along the Mediterranean Sea. The exact etiology of BD has not been fully explained yet, but the disease occurrence is associated with a genetic factor, human leukocyte antigen (HLA)-B51 antigen. Among the various immunodysfunctions that are found in BD, patients are increased neutrophil motility and superoxide production, as well as elevated production of tumor necrosis factor (TNF)-α and decreased production of interleukin (IL)-10. Elevated levels of inflammatory cytokines like IL-1 and IL-17 in BD have been found associated with aberrant expression of microRNA. Gene polymorphisms in BD patients have been observed in molecules involved in responses to pathogens that can ultimately modulate the host antimicrobial response. Moreover, several single nucleotide polymorphisms (SNPs) have been reported in genes encoding chemokines and adhesion molecules; many of these changes manifest as increases in vascular inflammation and vascular damage. Lastly, genetic and epigenetic changes have been suggested as involved in the pathogenesis of BD. Modifications in DNA methylation have been found in BD patient monocytes and lymphocytes, leading to adverse function of these cells. This review presents a comprehensive compilation of the literature with regard to the immunodysfunction underlying BD, as well as of the genetics, newly described clinical specifications and novel treatment strategies using immunomodulants based on the current understanding of BD.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"14 1","pages":"137-151"},"PeriodicalIF":3.3,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/1547691X.2017.1346008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35156286","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":"Safety of a proteoliposome from Neisseria meningitides as adjuvant for a house dust mite allergy vaccine.","authors":"Wendy Ramírez,&nbsp;Virgilio Bourg,&nbsp;Damaris Torralba,&nbsp;Elisa Facenda,&nbsp;Beatriz Tamargo,&nbsp;Bárbara O González,&nbsp;Gustavo Sierra,&nbsp;Oliver Pérez,&nbsp;Yordanis Perez-Llano,&nbsp;Alexis Labrada","doi":"10.1080/1547691X.2017.1346007","DOIUrl":"https://doi.org/10.1080/1547691X.2017.1346007","url":null,"abstract":"<p><p>The proteoliposome (PL) of Neisseria meningitidis serogroup B has been reported as a safe and potent vaccine adjuvant, inducing a T_H1-skewed response. The present study describes a pre-clinical safety evaluation of an allergy therapeutic vaccine candidate based on purified allergens from Dermatophagoides siboney house dust mite and PL as adjuvant, both components adsorbed onto aluminum hydroxide gel. Two separate studies of acute toxicity evaluation were performed in mice and rabbits, and two repeat-dose studies were conducted in non-sensitized and allergen-sensitized Balb/c mice, respectively. The study in sensitized mice intends to model a therapeutic setting. Aerosolized allergen challenge was used in both settings to model natural respiratory exposure. In the therapeutic setting, mice were administered with three doses containing 2 μg allergen at weekly intervals [subcutaneous route] and subsequently challenged with aerosolized allergen for 6 consecutive days. Parameters of general toxicity effects were assessed via measures of behavior, body weight, food and water consumption, and macroscopic evaluation of organs. Histological examination of organs and the injection site was performed. Potential immunotoxicity effects at the systemic level were assessed by blood eosinophil counting and serum allergen specific IgE by ELISA The vaccine did not produce general or functional toxic effects of significance, at a dose up to 100 μg allergen per kg body weight. An expected local reaction at the injection site was observed, which could be attributed mostly to the immunological effect of aluminum hydroxide. The models implemented here suggest an acceptable safety profile of this vaccine for testing in clinical trials of allergy immunotherapy.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"14 1","pages":"152-159"},"PeriodicalIF":3.3,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/1547691X.2017.1346007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35160061","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 in situ cytokine and leukocyte responses to acute smoking.","authors":"Tegan Kastelein,&nbsp;Rob Duffield,&nbsp;Frank Marino","doi":"10.1080/1547691X.2017.1332699","DOIUrl":"https://doi.org/10.1080/1547691X.2017.1332699","url":null,"abstract":"<p><p>This study examined immune/inflammatory parameters following an acute tobacco smoking episode in smokers with varying smoking histories. Twenty-eight male habitual smokers were categorized according to smoking history, e.g. younger smoker (YSM) or middle-aged smoker (MSM). Participants were matched for fitness and smoking habits and following baseline testing, undertook a smoking protocol involving consumption of two cigarettes within 15 min. Venous blood was collected pre- and immediately, 1 h, and 4 h post-protocol to permit analyses of circulating levels of interleukin (IL)-6, IL-1β, IL-1ra, monocyte chemoattractant protein-1 (MCP-1), C-reactive protein (CRP), and leukocytes. No baseline differences were observed between groups for IL-1ra, IL-1β, or leukocytes. MCP-1 and IL-6 levels were significantly (p < 0.05) elevated at baseline in YSM. Both groups showed an increase in MCP-1 levels from pre- to immediately post-cigarette consumption. The MSM also displayed an increase in IL-6 post-smoking, followed by a decline over the period from 1 to 4 h thereafter. A significant decline in circulating lymphocyte and eosinophil levels from immediately post-cigarette consumption to 1 h later was observed in both groups. Monocyte levels in the YSM followed a similar profile but no significant effects on this cell type were evident in the MSM. From these results, a 10-year difference in smoking history induces mild leukopenia. Altered responses due to smoking were also evident with respect to levels of circulating biomarkers, which may be indicative of an effect of differences in cumulative smoking history.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"14 1","pages":"109-115"},"PeriodicalIF":3.3,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/1547691X.2017.1332699","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35031908","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 immunomodulatory effects of zearalenone in mice.","authors":"Mohammad Rafiqul Islam,&nbsp;Jong Won Kim,&nbsp;Yoon-Seok Roh,&nbsp;Jong-Hoon Kim,&nbsp;Kang Min Han,&nbsp;Hyung-Joo Kwon,&nbsp;Chae Woong Lim,&nbsp;Bumseok Kim","doi":"10.1080/1547691X.2017.1340371","DOIUrl":"https://doi.org/10.1080/1547691X.2017.1340371","url":null,"abstract":"<p><p>Zearalenone (ZEA) is a non-steroidal estrogenic mycotoxin produced by Fusarium species. The toxicity of ZEA has been evaluated for reproductive and developmental effects; however, there is little evidence about its acute toxicity or general immunotoxicity. In the present study, immune regulatory functions were investigated in mice that had been exposed to ZEA (5 or 20 mg/kg BW) daily for 14 days. Results showed that sub-populations of CD4⁺, CD8⁺ and CD11c⁺ cells in the spleen and CD4⁺, CD8⁺ and F4/80⁺ cells in the mesenteric lymph nodes (MLN) of ZEA (20 mg/kg)-exposed hosts were decreased compared to those in the control mice. However, CD19⁺ and CD11c⁺ cells were increased in the MLN of the ZEA mice and CD4⁺CD25⁺Foxp3⁺ cells were decreased in the spleen and MLN. There were differential changes in the immune cell populations of the small intestine of the ZEA mice as well, depending on small intestine location. In ex vivo experiments, ZEA treatments resulted in increased proliferative capacities of mitogen-induced splenocytes and MLN cells; such changes were paralleled by significant increases in interferon (IFN)-γ production. With regard to serum isotypes, IgM levels were decreased and IgE levels were increased in the 20 mg/kg ZEA-treated mice. Mucosal IgA levels were decreased in the duodenum and vagina of these hosts. Serum analyzes also revealed that tumor necrosis factor (TNF)-α levels were decreased and interleukin (IL)-6 levels increased as a result of ZEA exposures. ZEA treatment also led to increased apoptosis in the spleen and Peyer's patches; these changes were associated with changes in the ratios of Bax:Bcl-2. Following priming with different TLR ligands, ZEA exposure led to differentially modulated TLR signaling and variable production of pro- and anti-inflammatory cytokines in RAW 264.7 macrophage cells. Taken together, these results indicated that ZEA could alter the normal expression/function of different immune system components and this would likely lead to immunomodulation in situ.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"14 1","pages":"125-136"},"PeriodicalIF":3.3,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/1547691X.2017.1340371","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35113103","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":"Correction to: Islam et al., Evaluation of immunomodulatory effects of zearalenone in mice.","authors":"","doi":"10.1080/1547691X.2017.1353242","DOIUrl":"https://doi.org/10.1080/1547691X.2017.1353242","url":null,"abstract":"","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"14 1","pages":"241"},"PeriodicalIF":3.3,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/1547691X.2017.1353242","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35162694","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 (BPA) aggravates multiple low-dose streptozotocin-induced Type 1 diabetes in C57BL/6 mice.","authors":"Marina Cetkovic-Cvrlje,&nbsp;Sinduja Thinamany,&nbsp;Kylie A Bruner","doi":"10.1080/1547691X.2017.1334722","DOIUrl":"https://doi.org/10.1080/1547691X.2017.1334722","url":null,"abstract":"<p><p>Type 1 diabetes (T1D) is a T-cell-mediated autoimmune disorder characterized by destruction of insulin-producing pancreatic β-cells. Whereas epidemiological data implicate environmental factors in the increasing incidence of T1D, their identity remains unknown. Though exposure to bisphenol A (BPA) has been associated with several disorders, no epidemiologic evidence has linked BPA exposure and T1D. The goal of this study was to elucidate diabetogenic potentials of BPA and underlying mechanisms in the context of T-cell immunity, in a multiple low-dose streptozotocin (MLDSTZ)-induced autoimmune mouse T1D model. C57BL/6 mice were orally exposed to 1 or 10 mg BPA/L starting at 4 wk of age; diabetes was induced at 9 wk of age with STZ. T-cell composition, function, and insulitis levels were studied at Days 11 and 50 during diabetes development (i.e. post-first STZ injection). Results showed both BPA doses increased diabetes incidence and affected T-cell immunity. However, mechanisms of diabetogenic action appeared divergent based on dose. Low-dose BPA fits a profile of an agent that exhibits pro-diabetogenic effects via T-cell immunomodulation in the early stages of disease development, i.e. decreases in splenic T-cell subpopulations [especially CD4⁺ T-cells] along with a trend in elevation of splenic T-cell formation of pro-inflammatory cytokines (IFN-γ, TNF-α, and IL-6). In contrast, high-dose BPA did not affect T-cell populations and led to decreased levels of IFN-γ and TNF-α. Both treatments did not affect insulitis levels at the disease early stage, but aggravated it later on. By the study end, besides decreasing T-cell proliferative capacity, low-dose BPA did not affect other T-cell-related parameters, including cytokine secretion, comparable to the effects of high-dose BPA. In conclusion, this study confirmed BPA as a potential diabetogenic compound with immunomodulatory mechanisms of action - in the context of T-cell immunity - that seemed to be dose dependent in the early immunopathogenesis of a MLDSTZ-induced model of T1D.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"14 1","pages":"160-168"},"PeriodicalIF":3.3,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/1547691X.2017.1334722","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35168186","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":"Celastrol attenuates impairments associated with lipopolysaccharide-induced acute respiratory distress syndrome (ARDS) in rats.","authors":"Yongjun Wei,&nbsp;Yu Wang","doi":"10.1080/1547691X.2017.1394933","DOIUrl":"https://doi.org/10.1080/1547691X.2017.1394933","url":null,"abstract":"<p><p>Celastrol, a constituent from a traditional Chinese medicinal herb belonging to the family Celastraceae, has been shown to impart anti-inflammatory properties, in part, by inhibiting NF-κB activity and related induction of pro-inflammatory cytokine formation/release. The present study investigated the effects of celastrol in an animal model of acute respiratory distress syndrome (ARDS) induced by intratracheal administration of lipopolysaccharides (LPSs). Celastrol pre-treatment groups received celastrol by intraperitoneal injection on seven consecutive days before LPS treatment. In rats evaluated 24 h after LPS administration, oxygenation indices and lung injury were measured, as were levels of inflammatory cells and cytokines in isolated bronchoalveolar lavage fluid (BALF). Lung tissue expression of proteins involved in NF-κB and ERK/MAPK pathways were measured by Western blot analyses. Celastrol pre-treatments appeared to attenuate LPS-induced lung injury and inflammatory responses in the rats, including decreases in inducible aggregationinfiltration of inflammatory cells and production/release of pro-inflammatory cytokines into the lung airways. Celastrol appeared to also inhibit NF-κB activation, but had no effect on ERK/MAPK pathways in the LPS-induced ARDS. The results here thus indicated that celastrol pre-treatment could impart protective effects against LPS-induced ARDS, and that these effects may be occurring through an inhibition of induction of NF-κB signaling pathways.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"14 1","pages":"228-234"},"PeriodicalIF":3.3,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/1547691X.2017.1394933","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35593081","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":"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}