Aryl Hydrocarbon Receptor is Involved in the Proinflammatory Cytokine Response to Cadmium.
2021
Authors:
Kulaš, JelenaTucović, Dina
Zeljković, Milica
Popović, Dušanka
Popov Aleksandrov, Aleksandra
Kataranovski, Milena
Mirkov, Ivana
Document Type:
Article (Published version)
,
©2021 by China CDC
Metadata
Show full item recordAbstract:
Objective To investigate involvement of the aryl hydrocarbon receptor (AhR) in the immunomodulatory effects of cadmium (Cd). Methods The effect of Cd on AhR activation ( CYP1A1 and CYP1B1 mRNA expression) was examined in lung leukocytes of Cd-exposed rats (5 and 50 mg/L, 30 d orally) and by in vitro leukocyte exposure. The involvement of AhR signaling in the effects of Cd on the interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF) lung leukocyte response was investigated in vitro using the receptor antagonist CH-223191. Results Cd increased CYP1B1 ( in vivo and in vitro) and CYP1A1 ( in vitro) mRNA, indicating AhR involvement in the action of Cd. In response to Cd, lung leukocytes increased IL-6 and decreased TNF at the gene expression and protein levels, but decreased IL-1β production due to reduced NLRP3. The AhR antagonist CH-223191 abrogated the observed effects of Cd on the cytokine response. The absence of AhR reactivity and cytokine response to Cd of leukocytes from the lungs of a rat strain that is less sensitive to Cd toxicity coincided with a high AhR repressor mRNA level. Conclusion AhR signaling is involved in the lung leukocyte proinflammatory cytokine response to Cd. The relevance of the AhR to the cytokine response to Cd provides new insight into the mechanisms of Cd immunotoxicity.
Keywords:
Aryl hydrocarbon receptor; Cadmium; Cytokine (IL-6; TNF; IL-1β) response; Lung leukocytesSource:
Biomedical and Environmental Sciences, 2021, 34, 3, 192-202Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200007 (University of Belgrade, Institute for Biological Research 'Siniša Stanković') (RS-MESTD-inst-2020-200007)
- Kementerian Pendidikan Malaysia
DOI: 10.3967/bes2021.025
ISSN: 0895-3988
PubMed: 33766215
WoS: 000642008600003
Scopus: 2-s2.0-85103341342
URI
http://www.besjournal.com/en/article/doi/10.3967/bes2021.025https://radar.ibiss.bg.ac.rs/handle/123456789/4191