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Updated: May 11, 2026
Expression, Purification, and Antimicrobial Activity of S100A12
Published on: May 13, 2017
Amyloid-β peptide-induced extracellular S100A9 depletion is associated with decrease of antimicrobial peptide
Eun Ok Lee1, Ji Hye Yang, Keun-A Chang
1Department of Microbiology, School of Medicine, Ewha Medical Research Institute, Ewha Womans University, 911-1, Mok-6-dong, Yangcheonku, Seoul 158-710, Republic of Korea.
Background:
S100A9 protein (myeloid-related protein MRP14, also referred to as calgranulin B) is a reliable marker of inflammation, an important proinflammatory factor of innate immunity and acts as an additional antimicrobial peptide in the innate immune system. Evidence indicates that S100A9 contributes to Alzheimer's disease (AD) pathology, although the precise mechanisms are not clear.
Methods:
We were interested to study the mechanisms of S100A9 release upon Aβ1-42 stimulation, the potential roles of extracellular S100A9 depletion in Aβ-induced cytotoxicity, and the interaction with innate immune response in THP-1 monocytic cells that have been challenged with mostly Aβ1-42 monomers instead of oligomers. We used protein preparation, Ca(2+) influx fluorescence imaging, MTT assay, siRNA knockdown, colony forming units (CFUs) assay and western blotting techniques to perform our study.
Results:
Aβ1-42 monomers elicited a marked decrease of S100A9 release into the cell culture supernatant in a dose-dependent manner in human THP-1 monocytes. This reduction of S100A9 release was accompanied by an increase of intracellular Ca(2+) level. Aβ1-42-mediated decrease of S100A9 release was not associated with Aβ1-42-induced cytotoxicity as measured by MTT reduction assay. This observation was confirmed with the recombinant S100A9, which had little effect on Aβ1-42-induced cytotoxicity. Moreover, depletion of S100A9 with siRNA did not significantly evoke the cell toxicity. On the other hand, Aβ1-42-induced extracellular S100A9 depletion resulted in decreased antimicrobial activity of the culture supernatant after Aβ1-42 stimulation. Immunodepletion of S100A9 with anti-S100A9 also decreased the antimicrobial peptide activity of the vehicle treated culture supernatant. Consistently, the recombinant S100A9 clearly elicited the antimicrobial peptide activity in vitro, confirming the observed antimicrobial activity of S100A9 in the culture supernatant.
Conclusion:
Collectively, our findings suggest that the mostly monomeric form of Aβ1-42 negatively regulates the innate immune system by down-regulating the secretion of S100A9, which is likely a main mediator of antimicrobial activity in the conditioned media of human THP-1 monocytes.
Insights
Amyloid-beta 1-42 monomers reduce S100A9 protein release, a key antimicrobial peptide, in monocytes. This down-regulation impairs the innate immune system's antimicrobial activity, suggesting a novel Alzheimer's disease mechanism.
Area of Science:
- Neuroimmunology
- Infectious Disease
Background:
- S100A9 protein is a key inflammatory marker and antimicrobial peptide.
- S100A9 is implicated in Alzheimer's disease (AD) pathology, but mechanisms are unclear.
Purpose of the Study:
- Investigate S100A9 release mechanisms upon amyloid-beta (Aβ) stimulation.
- Determine the role of extracellular S100A9 in Aβ-induced cytotoxicity and innate immune response.
Main Methods:
- THP-1 monocytes were stimulated with Aβ1-42 monomers.
- Techniques included Ca(2+) imaging, MTT assays, siRNA knockdown, and antimicrobial activity assays.
Main Results:
- Aβ1-42 monomers decreased S100A9 release and increased intracellular Ca(2+).
- This decrease did not correlate with cytotoxicity; S100A9 depletion showed minimal toxicity.
- Extracellular S100A9 depletion reduced antimicrobial activity, while recombinant S100A9 enhanced it.
Conclusions:
- Monomeric Aβ1-42 negatively regulates the innate immune system by reducing S100A9 secretion.
- S100A9 is a primary mediator of antimicrobial activity in monocyte-conditioned media.
