Proinflammatory effects of S100A8/A9 via TLR4 and RAGE signaling pathways in BV-2 microglial cells

Ma, Li; Sun, Peng; Zhang, Jiancheng; Zhang, Qing; Yao, Shanglong

doi:10.3892/ijmm.2017.2987

Cited by 114 publications

(88 citation statements)

References 46 publications

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“…Besides classical S100A8/A9 receptors, toll-like receptor 4 (TLR4) 4,5 and receptor for advanced glycation end products (RAGE), 5,6 we have reported the presence of the important novel receptors including extracellular matrix metalloproteinase inducer (EMMPRIN), neuroplastin (NPTN)α and β, melanoma cell adhesion molecule (MCAM) and activated leukocyte cell adhesion molecule (ALCAM). [7][8][9][10][11][12] Among these receptors, we found that lung cancer cell lines highly express NPTNβ compared with normal cells lines ( Figure S1A).…”

Section: Nptn and S100a8/a9 Are Highly Expressed In Lung Cancermentioning

confidence: 99%

“…This phenomenon is linked to the formation of a pre‐metastatic immunosuppressive environment and acts on chemotactic attraction of the remote cancer cells to the lung area . It has been reported that toll‐like receptor 4 (TLR4) and receptor for advanced glycation end products (RAGE) behave as receptors for S100A8/A9 . However, it is hard to explain the S100A8/A9‐related metastatic phenomena in a variety of cancer cells by only two types of receptors.…”

Section: Introductionmentioning

confidence: 99%

“…[4][5][6][7][8][9][10] Induction and secretion of the protein closely associated with several inflammatory settings including a cancermediated inflammatory setting. [4][5][6][7][8][9][10][11] Accumulating evidence indicates that induction of S100A8/A9 at a significant level readily occurs in lung tissue even when cancer cells appear in a region distant from the lung and that the induction of S100A8/A9 results in lung metastasis of cancer cells and their subsequent development in the inflammatory lung. 8,13 That evidence suggests that lung cancer may be greatly affected by just surrounding S100A8/A9, which is linked to the acquisition of a malignant phenotype in cancer cells in a short period of time.…”

Section: Introductionmentioning

confidence: 99%

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Neuroplastin‐β mediates S100A8/A9‐induced lung cancer disseminative progression

Sumardika

Chen

Tomonobu

et al. 2019

Molecular Carcinogenesis

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Compiling evidence indicates an unusual role of extracellular S100A8/A9 in cancer metastasis. S100A8/A9 secreted from either cancer cells or normal cells including epithelial and inflammatory cells stimulates cancer cells through S100A8/A9 sensor receptors in an autocrine or paracrine manner, leading to cancer cell metastatic progression. We previously reported a novel S100A8/A9 receptor, neuroplastin‐β (NPTNβ), which plays a critical role in atopic dermatitis when it is highly activated in keratinocytes by an excess amount of extracellular S100A8/A9 in the inflammatory skin lesion. Interestingly, our expression profiling of NPTNβ showed significantly high expression levels in lung cancer cell lines in a consistent manner. We hence aimed to determine the significance of NPTNβ as an S100A8/A9 receptor in lung cancer. Our results showed that NPTNβ has strong ability to induce cancer‐related cellular events, including anchorage‐independent growth, motility and invasiveness, in lung cancer cells in response to extracellular S100A8/A9, eventually leading to the expression of a cancer disseminative phenotype in lung tissue in vivo. Mechanistic investigation revealed that binding of S100A8/A9 to NPTNβ mediates activation of NFIA and NFIB and following SPDEF transcription factors through orchestrated upstream signals from TRAF2 and RAS, which is linked to anchorage‐independent growth, motility and invasiveness. Overall, our results indicate the importance of the S100A8/A9‐NPTNβ axis in lung cancer disseminative progression and reveal a pivotal role of its newly identified downstream signaling, TRAF2/RAS‐NFIA/NFIB‐SPDEF, in linking to the aggressive development of lung cancers.

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Section: Nptn and S100a8/a9 Are Highly Expressed In Lung Cancermentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Neuroplastin‐β mediates S100A8/A9‐induced lung cancer disseminative progression

Sumardika

Chen

Tomonobu

et al. 2019

Molecular Carcinogenesis

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“…The elevated concentrations of S100A8 and A9 in gingival crevicular fluid (GCF) correlated with periodontal inflammation (Haririan et al, 2016;Kajiura et al, 2017;Ren et al, 2009). These proteins are important pro-inflammatory mediators in acute and chronic inflammations (Ma, Sun, Zhang, Zhang, & Yao, 2017). Moreover, S100A9 showed anti-inflammatory effect on mice by deactivation of activated peritoneal macrophages (Aguiar-Passeti, Postol, Sorg, & Mariano, 1997).…”

mentioning

confidence: 99%

Salivary S100 proteins screen periodontitis among Korean adults

Karna

Kim

2019

J Clinic Periodontology

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Aim This study aims to evaluate the association of salivary S100A8 and A9 proteins with periodontitis and its screening ability for periodontitis cross‐sectionally. Material and Methods We selected 326 participants from the Yangpyeong Cohort: 218 participants with periodontitis and 108 participants without periodontitis. Stage II‐IV periodontitis according to the modification of new international classification of periodontitis was considered as periodontitis. S100A8 and A9 were assayed using enzyme‐linked immunosorbent assay kit. Age, sex, education, smoking, drinking, exercise, and metabolic syndrome were factored as confounders. Analyses of covariance and logistic regression analysis were applied to evaluate the association of S100A8 and A9 with periodontitis. Receiver operating characteristic curve was applied for screening ability. Results Those with periodontitis compared to those without periodontitis showed higher adjusted amount of S100A8 (3694 versus 6757 ng/ml, p < 0.001), but less adjusted amount of S100A9 (1341 versus 1030 ng/ml, p = 0.015). The screening ability of S100A8 and A9 on periodontitis was c‐statistics of 0.69 (p < 0.001) for both S100A8 and A9, 0.67 for S100A8 and 0.63 (p < 0.001) for S100A9. Conclusions Overall, salivary S100A8 and S100A9 could be practical markers for periodontitis. Its screening ability for periodontitis could be beneficial in clinics and at home.

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“…S100A8 itself is now considered a potent DAMP and has been reported to signal through TLR4 and/or RAGE to drive pro‐inflammatory mediator production . In our hands, recombinant S100A8 (1 μg/ml) drove robust pro‐IL‐1β expression at both the RNA and protein level (Fig.…”

Section: Resultsmentioning

confidence: 62%

S100A8 acts as an autocrine priming signal for heme-induced human Mϕ pro-inflammatory responses in hemolytic inflammation

Silveira

Mahon

Cunningham

et al. 2019

Journal of Leukocyte Biology

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Intravascular hemolysis, in addition to reducing red cell counts, incurs extensive vascular inflammation and oxidative stress. One product of hemolysis, heme, is a potent danger associated molecular pattern (DAMP), activating leukocytes and inducing cytokine expression and processing, among other pro-inflammatory effects. We explored pathways by which heme-induced inflammation may be amplified under sterile conditions. Incubation of human M s, differentiated from CD14 + cells, with heme induced time-and concentration-dependent gene and protein expression of S100A8, a myeloid cell-derived alarmin. Human M stimulation with recombinant S100A8, in turn, induced robust pro-IL-1 expression that was dependent upon NF-B activation, gene transcription, and partially dependent upon TLR4-mediated signaling. Moreover, heme itself stimulated significant M pro-IL-1 gene and protein expression via an S100A8-mediated mechanism and greatly amplified S100A8-driven NLRP3 inflammasome-mediated IL-1 secretion. In vivo, induction of acute intravascular hemolysis in mice induced a rapid elevation of plasma S100A8 that could be abolished by hemopexin, a heme scavenger. Finally, plasma S100A8 levels were found to be significantly elevated in patients with the inherited hemolytic anemia, sickle cell anemia, when compared with levels in healthy individuals. In conclusion, we demonstrate that hemolytic processes are associated with S100A8 generation and that some of the inflammatory effects of heme may be amplified by autocrine S100A8 production. Findings suggest a mechanism by which hemolytic inflammation could be propagated via leukocyte priming by endogenous proteins, even in sterile inflammatory environments such as those that occur in the hemolytic diseases. S100A8 may represent a therapeutic target for reducing inflammation in hemolytic disorders.

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Proinflammatory effects of S100A8/A9 via TLR4 and RAGE signaling pathways in BV-2 microglial cells

Cited by 114 publications

References 46 publications

Neuroplastin‐β mediates S100A8/A9‐induced lung cancer disseminative progression

Neuroplastin‐β mediates S100A8/A9‐induced lung cancer disseminative progression

Salivary S100 proteins screen periodontitis among Korean adults

S100A8 acts as an autocrine priming signal for heme-induced human Mϕ pro-inflammatory responses in hemolytic inflammation

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