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Open AccessJournal ArticleDOI

S100A8/A9 in Inflammation.

TLDR
A comprehensive and detailed overview of the distribution and biological functions of S100A8/A9 is provided and its application as a diagnostic and therapeutic target in inflammation-associated diseases is highlighted.
Abstract
S100A8 and S100A9 (also known as MRP8 and MRP14, respectively) are Ca2+ binding proteins belonging to the S100 family. They often exist in the form of heterodimer, while homodimer exists very little because of the stability. S100A8/A9 is constitutively expressed in neutrophils and monocytes as a Ca2+ sensor, participating in cytoskeleton rearrangement and arachidonic acid metabolism. During inflammation, S100A8/A9 is released actively and exerts a critical role in modulating the inflammatory response by stimulating leukocyte recruitment and inducing cytokine secretion. S100A8/A9 serves as a candidate biomarker for diagnosis and follow-up as well as a predictive indicator of therapeutic responses to inflammation-associated diseases. As blockade of S100A8/A9 activity using small-molecule inhibitors or antibodies improves pathological conditions in murine models, the heterodimer has potential as a therapeutic target. In this review, we provide a comprehensive and detailed overview of the distribution and biological functions of S100A8/A9 and highlight its application as a diagnostic and therapeutic target in inflammation-associated diseases.

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Elevated Calprotectin and Abnormal Myeloid Cell Subsets Discriminate Severe from Mild COVID-19.

TL;DR: It is shown that calprotectin plasma level and a routine flow cytometry assay detecting decreased frequencies of non-classical monocytes could discriminate patients who develop a severe COVID-19 form, suggesting a predictive value that deserves prospective evaluation.
Journal ArticleDOI

Sexual-dimorphism in human immune system aging.

TL;DR: Gene expression, chromatin state and immune subset composition in the blood of healthy humans 22 to 93 years of age is characterized, uncovering shared as well as sex-unique alterations, and a web resource is created to interactively explore the data.
Journal ArticleDOI

Plasma Proteomics Identify Biomarkers and Pathogenesis of COVID-19.

TL;DR: A machine learning-based pipeline was developed to identify 11 proteins as biomarkers and a set of biomarker combinations, which were validated by an independent cohort and accurately distinguished and predicted COVID-19 outcomes.
References
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Journal ArticleDOI

Alzheimer's Disease: Genes, Proteins, and Therapy

TL;DR: Evidence that the presenilin proteins, mutations in which cause the most aggressive form of inherited AD, lead to altered intramembranous cleavage of the beta-amyloid precursor protein by the protease called gamma-secretase has spurred progress toward novel therapeutics and provided discrete biochemical targets for drug screening and development.
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Mrp8 and Mrp14 are endogenous activators of Toll-like receptor 4, promoting lethal, endotoxin-induced shock

TL;DR: It is demonstrated that mice lacking Mrp8-Mrp14 complexes are protected from endotoxin-induced lethal shock and Escherichia coli–induced abdominal sepsis, indicating new inflammatory components that amplify phagocyte activation during sepsi upstream of TNFα–dependent effects.
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Metal Chelation and Inhibition of Bacterial Growth in Tissue Abscesses

TL;DR: It is demonstrated that calprotectin is a critical factor in the innate immune response to infection and metal chelation as a strategy for inhibiting microbial growth inside abscessed tissue is defined.
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Proinflammatory Activities of S100: Proteins S100A8, S100A9, and S100A8/A9 Induce Neutrophil Chemotaxis and Adhesion

TL;DR: S100A8, S100A9, and S 100A8/A9 are potent stimulators of neutrophils and strongly suggest that these proteins are involved in neutrophil migration to inflammatory sites.
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Nutritional immunity beyond iron: a role for manganese and zinc

TL;DR: Limiting the availability of zinc and manganese as a mechanism to defend against infection expands the spectrum of nutritional immunity and further establishes metal sequestration as a key defense against microbial invaders.
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