Immunomodulatory properties of HYCOs, NRF2 activators that simultaneously release carbon monoxide (CO) to cells and tissues
2023
Authors:
Stegnjaić, GoranMićanović, Dragica
Nikolovski, Neda
Momčilović, Miljana
Saksida, Tamara
Foresti, Roberta
Motterlini, Roberto
Miljković, Đorđe
Document Type:
Conference object (Published version)
,
©2023 BenBedPhar Consortium
Metadata
Show full item recordAbstract:
HYCOs are a novel class of hybrid compounds consisting of fumaric esters conjugated to
carbon monoxide-releasing molecules (CO-RMs). They were designed based on the
consideration that fumaric esters are known to activate the transcription factor Nrf2 and that
CO possesses potent anti-inflammatory properties. The dual action of these hybrids has
shown promising therapeutic effects. in animal models of psoriasis and multiple sclerosis.
We have recently started with the group of Drs Motterlini and Foresti in France a
collaborative research project relevant to the BenBedPhar COST Action, focusing on the
immunomodulatory effects of HYCOs. These effects were examined in vitro in cultures of
myeloid-derived cells (macrophages and dendritic cells), lymph node cells, immune cells
isolated from the inflamed central nervous system, and microglia. By assessing the
production of immunoactive molecules, including nitric oxide, reactive oxygen species and
cytokines, we provide evidence that HYCOs display immunomodulatory effects in all cell
populations examined in vitro. Moreover, we were able to demonstrate that HYCOs are
efficient in ameliorating type 1 diabetes in an animal model of this autoimmune disease. Our
results indicate that HYCOs are Nrf2 activators with promising immunomodulatory
therapeutic properties.
Funding / 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)
In:
- 5th Scientific Meeting of the COST Action CA20121: Bench to Bedside Transition for Pharmacological Regulation of NRF2 in non-communicable diseases (BenBedPhar): Translating NRF2 Research into Clinical Practice; 2023 Oct 12-13; Graz, Austria. BenBedPhar Consortium, 2023. p. 21.