2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced aryl hydrocarbon receptor activation enhanced the suppressive function of mesenchymal stem cells against splenocyte proliferation

In Vitro Cellular & Developmental Biology. Animal
Guorui ZhangXuejun Guo

Abstract

The immunosuppressive function of mesenchymal stem cells (MSCs) is well known. Aryl hydrocarbon receptor (AhR), a transcription factor of the bHLH/PAS family, is widely expressed in several cells and is involved in various physiological and pathological processes. Previously, we found that the expression of AhR was downregulated in MSCs isolated from mice with neutrophilic asthma and that the activation of AhR enhanced the function of MSCs to alleviate neutrophilic asthma. We hypothesized that AhR activation enhanced MSCs for their immunosuppressive function. We aimed to investigate whether AhR activation can augment the suppressive function of MSCs against splenocyte proliferation. We co-cultured MSCs or AhR-activated MSCs with splenocytes at different ratios. The results showed that AhR activation in MSCs upregulated the expression of inducible nitric oxide (iNOS), which promoted the production of nitric oxide (NO), thus enhancing the inhibitory effect on splenocyte proliferation. The NO donor S-nitroso-N-acetylpenicillamine also inhibited the proliferation of splenocytes, and the iNOS inhibitor N(G)-nitro L-arginine methyl ester and NO scavenger 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide partially reversed the im...Continue Reading

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Citations

Aug 14, 2020·International Journal of Molecular Sciences·Carrie Hayes SutterThomas R Sutter
Nov 26, 2020·International Journal of Molecular Sciences·Odile Poulain-GodefroyPatricia de Nadai

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Methods Mentioned

BETA
fluorescence-activated cell sorting
density gradient centrifugation
FACS
protein assay
PCR
ubiquitination
bronchoalveolar lavage

Software Mentioned

Image Lab
SPSS Statistics

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