The neonicotinoid insecticide Clothianidin adversely affects immune signaling in a human cell line.
Gennaro Di PriscoMarco IannacconeFlora IannielloRosalba FerraraEmilio CaprioFrancesco PennacchioRosanna CapparelliPublished in: Scientific reports (2017)
Clothianidin is a widely used neonicotinoid insecticide, which is a potent agonist of the nicotinic acetylcholine receptor in insects. This neurotoxic compound has a negative impact on insect immunity, as it down-regulates the activation of the transcription factor NF-κB. Given the evolutionary conserved role of NF-κB in the modulation of the immune response in the animal kingdom, here we want to assess any effect of Clothianidin on vertebrate defense barriers. In presence of this neonicotinoid insecticide, a pro-inflammatory challenge with LPS on the human monocytic cell line THP-1 results both in a reduced production of the cytokine TNF-α and in a down-regulation of a reporter gene under control of NF-κB promoter. This finding is corroborated by a significant impact of Clothianidin on the transcription levels of different immune genes, characterized by a core disruption of TRAF4 and TRAF6 that negatively influences NF-κB signaling. Moreover, exposure to Clothianidin concurrently induces a remarkable up-regulation of NGFR, which supports the occurrence of functional ties between the immune and nervous systems. These results suggest a potential risk of immunotoxicity that neonicotinoids may have on vertebrates, which needs to be carefully assessed at the organism level.
Keyphrases
- transcription factor
- signaling pathway
- lps induced
- aedes aegypti
- endothelial cells
- pi k akt
- nuclear factor
- immune response
- genome wide
- genome wide identification
- oxidative stress
- inflammatory response
- dna methylation
- induced pluripotent stem cells
- rheumatoid arthritis
- risk assessment
- pluripotent stem cells
- anti inflammatory
- toll like receptor
- dendritic cells
- climate change
- cell proliferation
- genome wide analysis