Implementation of this project will deliver a versatile screening platform for anti-inflammatory compounds and a list of validated small molecules with anti-inflammatory properties, which can be easily translated to pre-clinical studies.

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2020:

-We have generated a reporter cell line for detection of the secretion of IL-1β from macrophages by using CRISPR/Cas9 technology for endogenous tagging at the endogenous genetic locus, which recapitulates the physiological response to PAMPs and DAMPs similar to the primary cells. 

-We initiated the studies for in silico screening a library of compounds with potential to block IL-1β

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2021: 

-We have characterised the reporter cell line in terms of tagged IL-1β expression and secretion and we have optimised the stimulation conditions to be able to detect the secretion of IL-1β form 96 well plates

-We optimised the protocol for inducing sepsis with LPS to mice 

-We finalised the the studies for in silico screening of the library of compounds with potential to block IL-1β

-We performed an in vitro screening for a library of compounds with potential anti-inflammatory activity and identified three potential hits, one of them with a good percent of IL-1β secretion inhibition

 

2022:

 -We have validated one compound identified by hight-throughput screening for its capacity to impair IL-1β secretion form primary macrophages 

- The validation studies in primary macrophages were confirmed by experiments using a mouse model for sepsis

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