Thiostrepton inhibits Toll-like receptors 7, 8 and 9 mediated inflammatory responses

Toll-like receptors (TLRs) play a key role in sensing pathogen-associated molecular patterns for initiating immune responses against microbial infections. Ten TLRs are identified in human cells. Of them, TLRs 7, 8 and 9 (TLR7-9) comprise a subfamily. Activation of these three TLRs has been linked to the pathogenesis of autoimmune diseases including psoriasis. Thus antagonists of these TLRs are being investigated for their therapeutic applications on these diseases. In an attempt to develop novel TLR7-9 inhibitors, we searched the Gene Expression Omnibus database for gene expression profiles in cells treated with bortezomib which is known as an inhibitor for TLR7-9. These profiles were then used as an input to screen the Connectivity Map database for chemical compounds with similar functions as bortezomib. The result suggest that the antibiotic thiostrepton could has similar function as bortezomib in inhibition of TLR7–9. Further studies showed that thiostrepton effectively inhibits TLR7–9 activation in ce...