Asthma is one of the most common respiratory diseases. Lack of response or poor adherence to corticosteroids demands the development of new drug candidates for asthma. Endogenous nucleosides could be potential options since uridine has been reported to have an anti-inflammatory effect in asthma model. However, its molecular pathways and whether other nucleosides have similar therapeutic effects remain untouched. Thus, we herein report our investigation into the anti-inflammatory effects of guanosine and uridine, and the related inner signaling pathways in asthma model. Present study shows that administration of guanosine or uridine can reduce lung inflammation in OVA-challenged mice. Total cell counts in BALF, cytokines such as IL-4, IL-6, IL-13, OVA-specific IgE and mRNA level of Cxcl1, Cxlc3, IL-17 and Muc5ac were decreased in asthmatic mice after treatment. Besides, the production of IL-6 in LPS/IFN-γ induced THP-1 cells was also decreased by both nucleosides. In vivo and in vitro expressions of key molecules in the MAPK and NF-κB pathways were reduced after the treatment of both compounds. These findings suggest that guanosine has a similar potential therapeutic value in asthma as uridine and they exert anti-inflammatory effects through suppression of the MAPK and NF-κB pathways.Copyright © 2021 Elsevier Ltd. All rights reserved.
Guanosine and uridine alleviate airway inflammation via inhibition of the MAPK and NF-κB signals in OVA-induced asthmatic mice.
