CoChat
Sign Up
Cited by 1,450S100 Proteins and AnnexinsBiomarkers in Disease MechanismsNeutrophil, Myeloperoxidase and Oxidative Mechanisms

The DOI matches its Crossref record; 165 of the 165 references it cites were found in a registry or an index.

S100A8/A9 in Inflammation

Open access
Wang, Siwen, Song, Rui, Wang, Ziyi, Jing, Zhaocheng, Wang, Shaoxiong, Ma, Jian·2018·Frontiers in Immunology
DOI 10.3389/fimmu.2018.01298PMC PMC6004386
Open this paper in CoChat — free accountOpen PDF

Abstract

S100A8 and S100A9 (also known as MRP8 ang 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.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3389/fimmu.2018.01298

Cites

165 of 165 references verified0 citation errors · 0 not checkable

Statistics

Figures

Figure 1 The binding of S100A8/A9 to toll-like receptor (TLR) 4 triggers the MyD88-dependent pathway, appearing to play a vital role in inflammation. MyD88 recruits and activates IRAKs and TRAF6, which activates TAK1 via a TAB-mediated method. The activation of TAK1 facilitates the phosphorylation and activation of IKK and MAPK. Activated IKK phosphorylates and ubiquitinates I-κB, resulting in the liberation of NF-κB from inhibition. NF-κB translocates to the nucleus and induces the expression of pro-inflammatory cytokines. MAPKs, including p38, JNK, and ERK, have been demonstrated to activate c-Jun and c-fos, which translocate to the nucleus and form heterodimer AP-1, another transcription factor. Moreover, MAPK pathways are also involved in S100A8/A9-induced NF-κB activation during inflammation. The upregulated expression of pro-inflammatory genes amplifies the inflammatory response and severely destructs tissues in inflammation-associated diseases.
Figure 1 The binding of S100A8/A9 to toll-like receptor (TLR) 4 triggers the MyD88-dependent pathway, appearing to play a vital role in inflammation. MyD88 recruits and activates IRAKs and TRAF6, which activates TAK1 via a TAB-mediated method. The activation of TAK1 facilitates the phosphorylation and activation of IKK and MAPK. Activated IKK phosphorylates and ubiquitinates I-κB, resulting in the liberation of NF-κB from inhibition. NF-κB translocates to the nucleus and induces the expression of pro-inflammatory cytokines. MAPKs, including p38, JNK, and ERK, have been demonstrated to activate c-Jun and c-fos, which translocate to the nucleus and form heterodimer AP-1, another transcription factor. Moreover, MAPK pathways are also involved in S100A8/A9-induced NF-κB activation during inflammation. The upregulated expression of pro-inflammatory genes amplifies the inflammatory response and severely destructs tissues in inflammation-associated diseases.CC BY · PubMed Central
Figure 2 The mitochondrial pathways of S100A8/A9-induced apoptosis. Cellular apoptosis is a cascade that involves a rapid drop in mitochondrial membrane potential. S100A8/A9 increases reactive oxygen species (ROS) production, resulting in the depolarization of mitochondrial membranes and subsequent inhibition of BNIP3, an atypical pro-apoptotic Bcl2-family member, and activation of Bak. After the translocation of Bak and BNIP3 in mitochondria, cytochrome C, Smac, and HtrA2 are concomitantly released from mitochondria into the cytoplasm. They activate caspase-3 in a direct way or in an IAPs-dependent manner to induce apoptosis. Abbreviations: iBNIP3, inhibited BNIP3; aBak, activated Bak.
Figure 2 The mitochondrial pathways of S100A8/A9-induced apoptosis. Cellular apoptosis is a cascade that involves a rapid drop in mitochondrial membrane potential. S100A8/A9 increases reactive oxygen species (ROS) production, resulting in the depolarization of mitochondrial membranes and subsequent inhibition of BNIP3, an atypical pro-apoptotic Bcl2-family member, and activation of Bak. After the translocation of Bak and BNIP3 in mitochondria, cytochrome C, Smac, and HtrA2 are concomitantly released from mitochondria into the cytoplasm. They activate caspase-3 in a direct way or in an IAPs-dependent manner to induce apoptosis. Abbreviations: iBNIP3, inhibited BNIP3; aBak, activated Bak.CC BY · PubMed Central

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 165 references

Cited by

Sorted by citations

Items 801–900 of 1,001

Related

See all

Metadata

Authors
Wang, S., Song, R., Wang, Z., Jing, Z., Wang, S., & Ma, J.
Affiliations
Central South University (CN)
Corresponding author
Ma, Jian
ORCID
Venue
Frontiers in Immunology
Publisher
Frontiers Media SA
Published
2018-06-11
Volume
9
Pages
1298-1298
ISSN
1664-3224 (ISSN-L)
DOI
10.3389/fimmu.2018.01298
PMC
PMC6004386
OpenAlex
W2808305854
Cited by
1,450
References
165
Citations by year
2026: 176 · 2025: 217 · 2024: 248 · 2023: 225 · 2022: 236 · 2021: 184 · 2020: 119 · 2019: 40 · 2018: 4
FWCI
8.53
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Immunology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Natural Science Foundation of China (81672889, 81472694)
  • Hunan Provincial Science and Technology Department (2016JC2035)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › S100 Proteins and Annexins
  • Life Sciences › Immunology and Microbiology › Immunology › Biomarkers in Disease Mechanisms
  • Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Keywords
S100A8/A9, S-100 protein, heterodimer, calcium-binding proteins, inflammation, neutrophils, monocytes, leukocyte recruitment, cytokine production, arachidonic acid metabolism, biomarkers, therapeutic target, small molecule inhibitors
MeSH terms
Animals, Disease Susceptibility, Gene Expression Regulation, Humans, Immunity, Inflammation, Biomarkers, Autoimmunity, Protein Transport, Calgranulin A, Calgranulin B, Host-Pathogen Interactions, Molecular Targeted Therapy

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review