S100A9/S100A8: Myeloid representatives of the S100 protein family as prominent players in innate immunity

Nacken, Wolfgang; Roth, Johannes; Sorg, Clemens; Kerkhoff, Claus

doi:10.1002/jemt.10299

Cited by 312 publications

(310 citation statements)

References 112 publications

(89 reference statements)

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“…The early involvement of iPLA 2 , a calcium-insensitive phospholipase A 2 that can release DHA (33), in AA release was recently demonstrated in acute pleural inflammation (34). In this respect, we found via proteomic analysis that S100A9, a known AA-binding protein (35), was present in the exudate within 2 h after initiation of inflammation and reached maximal at the onset of R i , paralleling the PMN infiltration time course (Figs. 2A and 3B).…”

Section: Discussionsupporting

confidence: 54%

See 1 more Smart Citation

Molecular Circuits of Resolution: Formation and Actions of Resolvins and Protectins

Bannenberg

Chiang

Ariel

et al. 2005

The Journal of Immunology

628

461

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The cellular events underlying the resolution of acute inflammation are not known in molecular terms. To identify anti-inflammatory and proresolving circuits, we investigated the temporal and differential changes in self-resolving murine exudates using mass spectrometry-based proteomics and lipidomics. Key resolution components were defined as resolution indices including Ψmax, the maximal neutrophil numbers that are present during the inflammatory response; Tmax, the time when Ψmax occurs; and the resolution interval (Ri) from Tmax to T50 when neutrophil numbers reach half Ψmax. The onset of resolution was at ∼12 h with proteomic analysis showing both haptoglobin and S100A9 levels were maximal and other exudate proteins were dynamically regulated. Eicosanoids and polyunsaturated fatty acids first appeared within 4 h. Interestingly, the docosahexaenoic acid-derived anti-inflammatory lipid mediator 10,17S-docosatriene was generated during the Ri. Administration of aspirin-triggered lipoxin A4 analog, resolvin E1, or 10,17S-docosatriene each either activated and/or accelerated resolution. For example, aspirin-triggered lipoxin A4 analog reduced Ψmax, resolvin E1 decreased both Ψmax and Tmax, whereas 10,17S-docosatriene reduced Ψmax, Tmax, and shortened Ri. Also, aspirin-triggered lipoxin A4 analog markedly inhibited proinflammatory cytokines and chemokines at 4 h (20–50% inhibition), whereas resolvin E1 and 10,17S-docosatriene’s inhibitory actions were maximal at 12 h (30–80% inhibition). Moreover, aspirin-triggered lipoxin A4 analog evoked release of the antiphlogistic cytokine TGF-β. These results characterize the first molecular resolution circuits and their major components activated by specific novel lipid mediators (i.e., resolvin E1 and 10,17S-docosatriene) to promote resolution.

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Section: Discussionsupporting

confidence: 54%

“…2A and 3B). S100A9 is a cytosolic PMN protein that can be secreted and exhibits potent actions on inflammatory cell recruitment (35). In addition, ␣ 1 - macroglobulin, similar to ␣ 2 -macroglobulin, binds several proteinases including tissue-plasminogen activator and promotes their clearance (36).…”

Section: Discussionmentioning

confidence: 99%

Molecular Circuits of Resolution: Formation and Actions of Resolvins and Protectins

Bannenberg

Chiang

Ariel

et al. 2005

The Journal of Immunology

628

461

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“…The S100 protein family, especially S100A8 (29) and S100A9 (27), are cytoplasmic EF-hand Ca 2ϩ -binding proteins (36), which are some of the ligands that have been linked to human inflammatory and neoplastic diseases (37). Thus, we sought to determine the levels of expression of S100 proteins and RAGE in the lungs of UG-KO mice.…”

Section: Elevated Levels Of Metastasis In the Lungs Of Mice Lacking Umentioning

confidence: 99%

Lack of an Endogenous Anti-inflammatory Protein in Mice Enhances Colonization of B16F10 Melanoma Cells in the Lungs

Saha

Lee

Zhang

et al. 2010

Journal of Biological Chemistry

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Emerging evidence indicates a link between inflammation and cancer metastasis, but the molecular mechanism(s) remains unclear. Uteroglobin (UG), a potent anti-inflammatory protein, is constitutively expressed in the lungs of virtually all mammals. UG-knock-out (UG-KO) mice, which are susceptible to pulmonary inflammation, and B16F10 melanoma cells, which preferentially metastasize to the lungs, provide the components of a model system to determine how inflammation and metastasis are linked. We report here that B16F10 cells, injected into the tail vein of UG-KO mice, form markedly elevated numbers of tumor colonies in the lungs compared with their wild type littermates. Remarkably, UG-KO mouse lungs overexpress two calcium-binding proteins, S100A8 and S100A9, whereas B16F10 cells express the receptor for advanced glycation end products (RAGE), which is a known receptor for these proteins. Moreover, S100A8 and S100A9 are potent chemoattractants for RAGE-expressing B16F10 cells, and pretreatment of these cells with a blocking antibody to RAGE suppressed migration and invasion. Interestingly, in UG-KO mice S100A8/S100A9 concentrations in blood are lowest in tail vein and highest in the lungs, which most likely guide B16F10 cells to migrate to the lungs. Further, B16F10 cells treated with S100A8 or S100A9 overexpress matrix metalloproteinases, which are known to promote tumor invasion. Most notably, the metastasized B16F10 cells in UG-KO mouse lungs express MMP-2, MMP-9, and MMP-14 as well as furin, a pro-protein convertase that activates MMPs. Taken together, our results suggest that a lack of an anti-inflammatory protein leads to increased pulmonary colonization of melanoma cells and identify RAGE as a potential anti-metastatic drug target.It is estimated that more than 90% of human cancer deaths result from metastasis (1-8), a complex process in which the cells from a primary tumor successfully invade and colonize a distant organ (6 -9). It has long been suspected that a functional relationship exists between inflammation and cancer. Indeed, in 1863, Virchow observed that cancer develops at locations where chronic inflammation is present. This hypothesis is partly based on his assumption that some substances that cause tissue injury and inflammation also enhance cell proliferation (10). Although it is clear now that proliferation alone does not account for cancer, the cause and effect relationship between inflammation and cancer is widely accepted. Nonetheless, many aspects of the molecular and cellular mechanisms that link inflammation, migration, and establishment of tumor colonies in a distant organ remain unresolved (5). Recently, it has been reported that a tumor microenvironment actively contributes to cancer initiation, progression, and metastasis (11, 12). It has also been suggested that reductions in the rates of cancer morbidity and mortality may be achieved by gaining greater understanding of the molecular mechanism(s) of tumor cell migration, invasion, and establishment of colonies (13). In this regard...

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“…S100A8 and S100A9 (S100A8/A9), a family of low-molecular-weight intracellular EF-hand motif calcium-binding proteins, are abundantly expressed in cells of the myeloid lineage, including monocytes and neutrophils and early-differentiation states of macrophages. These proteins function predominantly as S100A8/A9 hetero-dimers and are highly chemotactic for leukocytes recruitment, adhesion and migration, thereby amplifying the local proinflammatory microenvironment (Nacken et al, 2003;Rychman et al, 2003). These proteins have been implicated in the inflammatory conditions such as rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, cystic fibrosis and psoriasis (Foell et al, 2007;Roth et al, 2001;2003).…”

Section: Introductionmentioning

confidence: 99%

S100A8 and S100A9 Promotes Invasion and Migration through p38 Mitogen-Activated Protein Kinase-Dependent NF-κB Activation in Gastric Cancer Cells

Kwon

Moon

Park

et al. 2013

Molecules and Cells

109

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S100A8 and S100A9 (S100A8/A9) are low-molecular weight members of the S100 family of calcium-binding proteins. Recent studies have reported S100A8/A9 promote tumorigenesis. We have previously reported that S100A8/A9 is mostly expressed in stromal cells and inflammatory cells between gastric tumor cells. However, the role of environmental S100A8/A9 in gastric cancer has not been defined. We observed in the present study the effect of S100A8/A9 on migration and invasion of gastric cancer cells. S100A8/ A9 treatment increased migration and invasionat lower concentrations that did not affect cell proliferation and cell viability. S100A8/A9 caused activation of p38 mitogenactivated protein kinase (MAPK) and nuclear factor-κB (NF-κB). The phosphorylation of p38 MAPK was not affected by the NF-κB inhibitor Bay whereas activation of NF-κB was blocked by p38 MAPK inhibitor SB203580, indicating that S100A8/A9-induced NF-κB activation is mediated by phosphorylation of p38 MAPK. S100A8/A9-induced cell migration and invasion was inhibited by SB203580 and Bay, suggesting that activation of p38 MAPK and NF-κB is involved in the S100A8/A9 induced cell migration and invasion. S100A8/A9 caused an increase in matrix metalloproteinase 2 (MMP2) and MMP12 expression, which were inhibited by SB203580 and Bay. S100A8/A9-induced cell migration and invasion was inhibited by MMP2 siRNA and MMP12 siRNA, indicating that MMP2 and MMP12 is related to the S100A8/A9 induced cell migration and invasion. Taken together, these results suggest that S100A8/A9 promotes cell migration and invasion through p38 MAPKdependent NF-κB activation leading to an increase of MMP2 and MMP12 in gastric cancer.

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S100A9/S100A8: Myeloid representatives of the S100 protein family as prominent players in innate immunity

Cited by 312 publications

References 112 publications

Molecular Circuits of Resolution: Formation and Actions of Resolvins and Protectins

Molecular Circuits of Resolution: Formation and Actions of Resolvins and Protectins

Lack of an Endogenous Anti-inflammatory Protein in Mice Enhances Colonization of B16F10 Melanoma Cells in the Lungs

S100A8 and S100A9 Promotes Invasion and Migration through p38 Mitogen-Activated Protein Kinase-Dependent NF-κB Activation in Gastric Cancer Cells

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