In:
Future Medicinal Chemistry, Future Science Ltd, Vol. 15, No. 6 ( 2023-03), p. 533-554
Abstract:
Background: Sepsis is a syndrome due to microbial infection causing impaired multiorgan function. Its underlying cause is immune dysfunction and macrophages play an essential role. Methods: TIRAP interaction with PKCδ in macrophage was studied, revealing downstream signaling by Western blot and quantitative reverse transcriptase PCR. Dorzolamide (DZD) disrupting TIRAP–PKCδ interaction was identified by virtual screening and validated in vitro and in septic mice. Results: The study highlights the indispensable role of TIRAP–PKCδ in p38 MAPK-activation, NF-κB- and AP-1-mediated proinflammatory cytokines expression, whereas DZD significantly attenuated the signaling. Conclusion: Targeting TIRAP–PKCδ interaction by DZD is a novel therapeutic approach for treating sepsis.
Type of Medium:
Online Resource
ISSN:
1756-8919
,
1756-8927
DOI:
10.4155/fmc-2022-0260
Language:
English
Publisher:
Future Science Ltd
Publication Date:
2023
SSG:
15,3
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