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Journal of Immunotoxicology

Mehrdad Ahadi, Haniyeh Ghasemian, Mahdi Behdani, Fatemeh Kazemi-Lomedasht
While monoclonal antibodies are efficient therapeutics for cancer treatment, nanobodies or variable heavy domain - due to their small size, high stability, and solubility - have many advantages in comparison. Oligoclonal nanobodies are a mixture of nanobodies against different epitopes of an antigen. Specific nanobodies against vascular endothelial growth factor (VEGF, which has an important role in cancer angiogenesis) were selected from an immune camel library using biopanning. Specific binding of the nanobodies to VEGF antigen was assessed by periplasmic extract enzyme-linked immunosorbent assay (ELISA)...
November 9, 2018: Journal of Immunotoxicology
Gregory S Ladics
An extensive safety assessment process exists for genetically-engineered (GE) crops. The assessment includes an evaluation of the introduced protein as well as the crop containing the protein with the goal of demonstrating the GE crop is "as-safe-as" non-GE crops in the food supply. One of the evaluations for GE crops is to assess the expressed protein for allergenic potential. Currently, no single factor is recognized as a predictor for protein allergenicity. Therefore, a weight-of-the-evidence approach, which accounts for a variety of factors and approaches for an overall assessment of allergenic potential, is conducted...
November 9, 2018: Journal of Immunotoxicology
Amy Sharma, Yoshiro Saito, Shuen-Iu Hung, Dean Naisbitt, Jack Uetrecht, Jeanine Bussiere
Current advances in the study of cutaneous adverse drug reactions can be attributed to the recent understanding that the skin is both a metabolically and immunologically competent organ. The ability of the skin to serve as a protective barrier with limited drug biotransformation ability, yet highly active immune function, has provided insights into its biological capability. While the immune response of the skin to drugs is vastly different from that of the liver due to evolutionary conditioning, it frequently occurs in response to various drug classes and manifests as a spectrum of hypersensitivity reactions...
October 14, 2018: Journal of Immunotoxicology
Ling Yang, Jiaxiang Zhang, Na Li, Haibo Xie, Shuangping Chen, Hui Wang, Tong Shen, Qi-Xing Zhu
Trichloroethylene (TCE) is known to induce skin disorders and multi-system dysfunction, but the mechanism of this multi-organ injury is not entirely clear. It was shown in a previous study that levels of pivotal end-products of the kallikrein-kinin system (KKS), i.e. bradykinin (BK) and BK receptors B1R/B2R, in the kidneys were increased by TCE exposure. Unfortunately, how BK and its receptors acted in the etiology of the induced renal injury is not clear. Thus, this study explored any correlation between BK receptors and immune renal injury in TCE-sensitized mice by blocking the BK receptors B1R/B2R...
December 2018: Journal of Immunotoxicology
Brendon Frank, Yu-Ling Wei, Kyung-Hoon Kim, Abraham Guerrero, Hervé Lebrec, Mercedesz Balazs, Xiaoting Wang
The immunotoxic potential of drug candidates is assessed through the examination of results from a variety of studies and endpoints. While the functional assessment of CD8+ cytotoxic T-lymphocytes (CTL) is well-characterized in the clinic, the lack of a robust macaque CTL functional assay has been an important hurdle in evaluating and accurately quantifying cell-mediated CD8+ T-cell effector responses in the nonclinical setting. This paper describes the development of an assay to measure CTL activity in peripheral blood mononuclear cells (PBMC) isolated from Cynomolgus macaques...
December 2018: Journal of Immunotoxicology
Lucie Leung-Gurung, Priscilla Escalante Cobb, Faraj Mourad, Cristina Zambrano, Zachary Muscato, Victoria Sanchez, Kanya Godde, Christine Broussard
Endocrine-disrupting chemicals (EDC) are widespread in the built and natural environments. Heightened public awareness of their potential danger has led to concern about whether EDC and their metabolites have significant negative biological effects. Studies have shown that EDC like DDT and other organochlorine pesticides, such as methoxychlor (MXC), have adverse effects on immune cells, but no studies have addressed the impact of HPTE, the primary metabolite of MXC. To elucidate the presence and significance of HPTE adverse effects, this study explored the impact of HPTE on a critical window and component of immune system development, embryonic T-cell development...
December 2018: Journal of Immunotoxicology
Yingjia Chen, Hannah Shibo Xu, Tai L Guo
The immunotoxicant bisphenol A (BPA) may produce toxic effects on organs and systems, in part, by altering the secretion of cytokines and chemokines. However, systematic studies of the effects of BPA, let alone of its analogs and in cases when there are interactions with other chemicals, on innate immunity and cytokine modulation are limited. The objectives of this study were to investigate the immunomodulatory effects of: (1) BPA and its analogs, BPS and BPAF; and (2) the interaction between BPA and genistein (GEN), a partial estrogen agonist or antagonist...
December 2018: Journal of Immunotoxicology
Alastair Mak, Tiffany Cho, Jack Uetrecht
Clinical evidence suggests that most idiosyncratic drug-induced liver injury (IDILI) is immune-mediated. The danger hypothesis suggests that liver injury and inflammation would increase the risk of an immune response leading to IDILI. Therefore, a reasonable hypothesis would be that an underlying chronic liver disease such as non-alcoholic steatohepatitis (NASH) would increase the risk of developing IDILI due to inflammation and release of danger signals from damaged cells. In order to test this hypothesis, mice were fed a methionine-/choline-deficient (MCD) diet that produces a consistent NASH phenotype, along with amodiaquine (AQ) - a drug known to cause IDILI in humans...
December 2018: Journal of Immunotoxicology
Weicheng Zhang, Libao Chen, Lunguang Yao
Skin sensitization is an important occupational health problem and immunotoxicity endpoint. Considering animal welfare and time and cost savings, many alternative approaches, such as those conducted in vitro, in silico, and in chemo, have been proposed and applied to predict skin sensitization of compounds. Toxicologically, sensitizers can elicit excess toxicity at greater levels than non-sensitizers due to their capacity to react with proteins/peptides. Based on this understanding, calculated toxicity enhancements (Te ) of 65 organic compounds from three in vitro bioassays, i...
December 2018: Journal of Immunotoxicology
Amy J Nelson, Shyamal K Roy, Kristi Warren, Katherine Janike, Geoffrey M Thiele, Ted R Mikuls, Debra J Romberger, Dong Wang, Benjamin Swanson, Jill A Poole
Skeletal health consequences associated with inflammatory diseases of the airways significantly contribute to morbidity. Sex differences have been described independently for lung and bone diseases. Repetitive inhalant exposure to lipopolysaccharide (LPS) induces bone loss and deterioration in male mice, but comparison effects in females are unknown. Using an intranasal inhalation exposure model, 8-week-old C57BL/6 male and female mice were treated daily with LPS (100 ng) or saline for 3 weeks. Bronchoalveolar lavage fluids, lung tissues, tibias, bone marrow cells, and blood were collected...
December 2018: Journal of Immunotoxicology
Min Liu, Hui Wang, Jiaxiang Zhang, Xiaodong Yang, Bodong Li, Changhao Wu, Qixing Zhu
Both NF-κB pathway and complement activation appear to be involved in kidney damage induced by trichloroethylene (TCE). However, any relationship between these two systems has not yet been established. The present study aimed to clarify the role of NF-κB in complement activation and renal injury in TCE-sensitized BALB/c mice. Mice were sensitized by an initial subcutaneous injection and repeated focal applications of TCE to dorsal skin at specified timepoints. NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) was injected (intraperitoneal) before the final two focal TCE challenges...
December 2018: Journal of Immunotoxicology
Eita Sasaki, Haruka Momose, Yuki Hiradate, Ken J Ishii, Takuo Mizukami, Isao Hamaguchi
Vaccines are inoculated in healthy individuals from children to the elderly, and thus high levels of safety and consistency of vaccine quality in each lot must meet the required specifications by using preclinical and lot release testing. Because vaccines are inoculated into humans, recapitulation of biological reactions in humans should be considered for test methods. We have developed a new method to evaluate the safety of influenza vaccines using biomarker gene expression in mouse and rat models. Some biomarker genes are already known to be expressed in human lymphocytes, macrophages and dendritic cells; therefore, we considered some of these genes might be common biomarkers for human and mice to evaluate influenza vaccine safety...
December 2018: Journal of Immunotoxicology
Rachel P Frawley, Matthew Smith, Mark F Cesta, Schantel Hayes-Bouknight, Chad Blystone, Grace E Kissling, Shawn Harris, Dori Germolec
Poly- and perfluoroalkyl substances (PFAS) are chemically and thermally stable, hydrophobic, lipophobic compounds used in stain repellants and water and oil surfactants, and associated with immunosuppression and peroxisome proliferator activity. Perfluoro-n-decanoic acid (PFDA, (CF3 (CF2 )8 COOH), a fluorinated straight chain fatty acid compound, is reported to induce thymic atrophy and reversible bone marrow hypocellularity in rodent models. The objective of this study was to assess potential immunotoxicity of PFDA, due to its structural similarity to other immunosuppressive PFASs...
December 2018: Journal of Immunotoxicology
Rie Yanagisawa, Eiko Koike, Tin-Tin Win-Shwe, Takamichi Ichinose, Hirohisa Takano
Benzo[a]pyrene (BaP) can induce developmental and reproductive toxicity; however, the full scope of its immunotoxic effects remains unknown. This study aimed to assess effects of lactational exposure to low-dose BaP (comparable to human exposure) on potential allergic\non-allergic immune responses in murine offspring. Lactating C3H/HeJ dams were orally dosed with BaP at 0, 0.25, 5.0, or 100 pmol/animal/week) at post-natal days [PND] 1, 8, and 15. Five-weeks-old pups then received intratracheally ovalbumin (OVA) every 2 weeks for 6 weeks...
December 2018: Journal of Immunotoxicology
Caterina Ledda, Rosario Caltabiano, Carla Loreto, Diana Cinà, Paola Senia, Andrea Musumeci, Vincenzo Ricceri, Cristoforo Pomara, Venerando Rapisarda
Fluoro-edenite (FE) is an asbestiform mineral fiber spotted in the lava rocks excavated from a stone quarry in Biancavilla (Italy). The derived material had been employed locally for building purposes. Previous studies found evidence that exposure to asbestos may induce autoimmunity, with frequency of anti-nuclear autoantibodies (ANA). The aim of this study was to explore the relationship between FE exposure and autoimmune responses in an exposed population. For the study, 60 subjects living in the area of Biancavilla and 60 subjects as control group were randomly invited to participate...
December 2018: Journal of Immunotoxicology
Eun-Jung Park, Timur O Khaliullin, Michael R Shurin, Elena R Kisin, Naveena Yanamala, Bengt Fadeel, Jaerak Chang, Anna A Shvedova
With the rapid development of synthetic alternatives to mineral fibers, their possible effects on the environment and human health have become recognized as important issues worldwide. This study investigated effects of four fibrous materials, i.e. nanofibrillar/nanocrystalline celluloses (NCF and CNC), single-walled carbon nanotubes (CNTs), and crocidolite asbestos (ASB), on pulmonary inflammation and immune responses found in the lungs, as well as the effects on spleen and peripheral blood immune cell subsets...
December 2018: Journal of Immunotoxicology
Francisco Gallardo-Vera, Miguel Tapia-Rodriguez, Daniel Diaz, Teresa Fortoul van der Goes, Luis F Montaño, Erika P Rendón-Huerta
Vanadium is an air pollutant that imparts immunosuppressive effects on NK cell immune responses, in part, by dysregulating interleukin (IL)-2/IL-2R-mediated JAK signaling pathways and inducing apoptosis. The aim of the present study was to evaluate effects of vanadium pentoxide (V2 O5 ) on other IL-2 receptor-mediated signaling pathways, i.e. PI3K-AKT-mTOR and Ras-MAPK. Here, IL-2-independent NK-92MI cells were exposed to different V2 O5 doses for 24 h periods. Expression of PI3K, Akt, mTOR, ERK1/2, MEK1, PTEN, SHP1, BAD and phosphorylated forms, as well as caspases-3, -8, -9, BAX and BAK in/on the cells were then determined by flow cytometry...
December 2018: Journal of Immunotoxicology
Connor F Laule, Cameron R Wing, Evan J Odean, Jacob A Wilcox, Jeffrey S Gilbert, Jean F Regal
Preeclampsia is a pregnancy-specific condition manifested by new-onset maternal hypertension with systemic inflammation, including increased innate immune system complement activation. While exact pathophysiology is unknown, evidence suggests that inadequate spiral artery invasion and resulting utero-placental insufficiency is the initiating event. Cigarette smoking during pregnancy decreases the risk of preeclampsia. Nicotine, a major component of cigarettes, stimulates the efferent cholinergic anti-inflammatory pathway through peripherally expressed nicotinic acetylcholine receptors (nAChR) and is known to attenuate ischemia-reperfusion injury in kidney and liver...
December 2017: Journal of Immunotoxicology
Yongjun Wei, Yu Wang
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...
December 2017: Journal of Immunotoxicology
Kelly A Shipkowski, Christopher M Sheth, Matthew J Smith, Michelle J Hooth, Kimber L White, Dori R Germolec
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...
December 2017: Journal of Immunotoxicology
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