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Polychlorinated Biphenyls (PCB 101, 153, and 180) Impair Murine Macrophage Responsiveness to Lipopolysaccharide: Involvement of NF-κB Pathway
- Source :
- Toxicological Sciences
- Publication Year :
- 2015
- Publisher :
- Oxford University Press (OUP), 2015.
-
Abstract
- Non-dioxin-like (NDL) polychlorinated biphenyls (PCBs) are persistent organic pollutants, associated with a range of adverse health effects, including interference with the immune system. In this study, we investigate the capability of NDL-PCBs 101, 153, and 180, 3 of the 6 NDL-PCBs defined as indicators, to impair the immune response in lipopolysaccharide (LPS)-activated J774A.1 and primary murine macrophages. Our results clearly demonstrate that the exposure of J774A.1 and primary macrophages to NDL-PCB 153 or 180 or all NDL-PCBs mixtures causes a significant reduction in LPS-induced cytokine/chemokine synthesis, such as tumor necrosis factor-α and interleukin-6, together with monocyte chemoattractant protein-1, involved in cell recruitment. Moreover, PCBs were found to suppress LPS-stimulated NO production, and to reduce cyclooxygenase-2 and inducible nitric oxide synthase expression in J774A.1 and primary macrophages. At mechanistic level, PCBs significantly counteract the LPS-driven toll-like receptor (TLR) 4 and CD14 upregulation, therefore inhibiting downstream nuclear factor-κB (NF-κB) activation in J774A.1. Furthermore, PCBs determine a significant loss of macrophage endocytic capacity, a prerequisite for efficient antigen presentation. Taken together, these data indicate that NDL-PCBs reduce macrophage responsiveness, particularly when they are combined at concentrations per se inactive, impairing the capability to orchestrate a proper immune response to an infectious stimulus, disrupting TLR4/NF-κB pathway.
- Subjects :
- Lipopolysaccharides
Male
Chemokine
Lipopolysaccharide
Cell Survival
medicine.medical_treatment
CD14
Primary Cell Culture
Antigen presentation
Lipopolysaccharide Receptors
Biology
Nitric Oxide
Toxicology
chemistry.chemical_compound
medicine
Animals
endocytosis
Rats, Wistar
NF-κB, toll-like receptor 4
Macrophages
Monocyte
lipopolysaccharide
NF-kappa B
Macrophage Activation
Polychlorinated Biphenyls
PCBs Disrupt Macrophage Response to LPS
Rats
Cell biology
Toll-Like Receptor 4
endocytosi
Cytokine
medicine.anatomical_structure
chemistry
Cyclooxygenase 2
Immunology
TLR4
biology.protein
Cytokines
Environmental Pollutants
Tumor necrosis factor alpha
immune suppression
Chemokines
non-dioxin-like polychlorinated biphenyls
Signal Transduction
Subjects
Details
- ISSN :
- 10960929 and 10966080
- Volume :
- 147
- Database :
- OpenAIRE
- Journal :
- Toxicological Sciences
- Accession number :
- edsair.doi.dedup.....3d97cf30e13eb743577118889be9b231