Figure - PMC

Skip to main content

An official website of the United States government

Here's how you know

Here's how you know

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

View full-text article in PMC

. 2022 Jun 20;11(12):1979. doi: 10.3390/cells11121979

Search in PMC
Search in PubMed
View in NLM Catalog
Add to search

© 2022 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

PMC Copyright notice

S100A8 and S100A9 are well known ligands of TLR4 and induce the expression of proinflammatory cytokines and type I interferons in monocytes and macrophages. Therefore, they function as amplifiers of phagocyte activation during the early hyper-inflammatory state of SIRS. However, long-term stimulation with S100A8/S100A9 has a regulatory role in promoting phagocyte hypo-responsiveness to subsequent inflammatory stimulation. It was shown that prolonged stimulation with low doses of S100A8 and S100A9 leads to an activation of the phosphatidylinositol 3-kinase/AKT/GSK-3β pathway which interferes with the NF-κB–driven expression of proinflammatory cytokines. This inhibition of cytokine production is further enhanced by secondary IL-10 triggered activation of STAT3 and BCL-3.