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Immunosuppressive effects of a CD4 receptor down-modulator: in vitro study of the signal peptide-dependent ER translocation inhibitor cyclotriazadisulfonamide (CADA) KU Leuven

Elisa Claeys
The small molecule cyclotriazadisulfonamide (CADA) was identified as an inhibitor of human immunodeficiency virus replication. It was shown that its antiviral potency is due to signal peptide-dependent inhibition of co-translational translocation of human CD4, the primary receptor for human immunodeficiency virus entry. The CD4 receptor plays an important role in the immune system, especially during activation of T cells by stabilizing the ...

Anticancer effects of ikarugamycin and astemizole identified in a screen for stimulators of cellular immune responses Universiteit Gent

Shuai Zhang, Liwei Zhao, Mengfei Guo, Peng Liu, Sijing Li, Wei Xie, Ai-Ling Tian, Jonathan G. Pol, Hui Chen, Hui Pan, et al.
Background: Most immunotherapies approved for clinical use rely on the use of recombinant proteins and cell-based approaches, rendering their manufacturing expensive and logistics onerous. The identification of novel small molecule immunotherapeutic agents might overcome such limitations. Method: For immunopharmacological screening campaigns, we built an artificial miniature immune system in which dendritic cells (DCs) derived from immature ...

Purinergic signaling in inflammatory cells: P2 receptor expression, functional effects, and modulation of inflammatory responses Universiteit Gent

Fenila Jacob, Claudina Perez Novo, Claus Bachert, Koen Van Crombruggen
Extracellular ATP and related nucleotides promote a wide range of pathophysiological responses via activation of cell surface purinergic P2 receptors. Almost every cell type expresses P2 receptors and/or exhibit regulated release of ATP. In this review, we focus on the purinergic receptor distribution in inflammatory cells and their implication in diverse immune responses by providing an overview of the current knowledge in the literature ...

The lymphocyte cytokinesis block micronucleus test in human populations occupationally exposed to vinyl chloride Vrije Universiteit Brussel

Claudia Bolognesi, Marco Bruzzone, Marcello Ceppi, Micheline Volders

Vinyl chloride (VC) is widely used in industry in the production of polyvinyl chloride (PVC), which is used to manufacture a large variety of materials. VC was classified as a known (Group 1) human carcinogen by IARC on the basis of increased risk for liver angiosarcoma and hepatocellular cancer, and the carcinogenicity of VC was shown to be mediated by a genotoxic mechanism. Following inhalation, the compound is rapidly absorbed and ...

Validity of the Lymphocyte Cytokinesis-Block Micronucleus Assay (L-CBMN) as biomarker for human exposure to chemicals with different modes of action Vrije Universiteit Brussel

Micheline Volders, Michael Fenech, Claudia Bolognesi

Recently fourteen systematic reviews applying the same selection and evaluation criteria analyzed the induction of micronuclei in lymphocytes as biomarker for DNA damage induced by human exposure to a given chemical or chemical mixture. The results obtained in the individual reviews were summarized to evaluate the validity of the Cytokinesis-Block-Micronucleus assay in lymphocytes (L-CBMN) and propose recommendations for its use in ...

The ex vivo L-CBMN assay detects significant human exposure to butadiene Vrije Universiteit Brussel

Claudia Bolognesi, Micheline Volders

1,3-Butadiene (BD), an important industrial chemical used in the production of synthetic rubber and resins and a ubiquitous environmental pollutant, was classified as a human carcinogen by IARC. BD requires metabolic activation to different epoxides that are known to bind to DNA, inducing also DNA-DNA and DNA-protein crosslinks. The DNA damage leading to mutations has been identified as the mode of action of BD. Experimental studies in ...

Molecular mechanisms by which in vivo exposure to exogenous chemical genotoxic agents can lead to micronucleus formation in lymphocytes in vivo and ex vivo in humans Vrije Universiteit Brussel

Michael Fenech, Siegfried Knasmueller, Claudia Bolognesi, Stefano Bonassi, Nina Holland, Lucia Migliore, Fabrizio Palitti, Adayapalam T Natarajan, Micheline Volders

The purpose of this review is to summarise current knowledge on the molecular mechanisms by which in vivo exposure to exogenous chemical genotoxins in humans induces micronuclei (MNi) and other nuclear anomalies in lymphocytes in vivo and ex vivo after nuclear division in vitro. MNi originate from acentric chromosome fragments and/or whole chromosomes that are unable to engage with the mitotic spindle and/or fail to segregate properly to the ...

Modulation of cytokine production by cyclic adenosine monophosphate analogs in human leukocytes Vrije Universiteit Brussel Universiteit Gent

Sarah Gerlo

Cyclic adenosine monophosphate (cAMP) is a well-known second messenger that operates through different signaling molecules, including protein kinase A (PKA) and guanine exchange proteins directly activated by cAMP (EPAC). Cell-permeable cAMP analogs such as 8-(4-chloro-phenyl-thio)-cAMP (8-pCPT-cAMP) modulate cytokine secretion by different leukocyte subsets, including T cells and monocytes. Since cAMP-modulating drugs such as ...

Thalidomide maintenance therapy maturates the T cell compartment and compromises antigen-specific antitumor immunity in patients with multiple myeloma Vrije Universiteit Brussel

Isabelle Herth, Mathias Witzens-Harig, Philipp Beckhove, Dirk Hose, Tobias Meissner, Brigitte Neuber, Melanie Engelhardt, Jürgen Haas, Kai Neben, Anthony D Ho, et al.

Interferon (INF)-α was the maintenance treatment of choice after autologous stem cell transplantation in multiple myeloma in the past, but currently Thalidomide is commonly used. In this prospective study, the implications of the various types of maintenance therapy on the patients T cell pattern and activation status were assessed. T cells were analyzed for expression of surface molecules, cytokine secretion, the presence of regulatory T ...

Chronic fatigue syndrome (CFS) Vrije Universiteit Brussel

Geir Bjørklund, Maryam Dadar, Joeri Pen, Salvatore Chirumbolo, Jan Aaseth

Chronic fatigue syndrome (CFS) is known as a multi-systemic and complex illness, which induces fatigue and long-term disability in educational, occupational, social, or personal activities. The diagnosis of this disease is difficult, due to lacking a proper and suited diagnostic laboratory test, besides to its multifaceted symptoms. Numerous factors, including environmental and immunological issues, and a large spectrum of CFS symptoms, have ...