S100A8-S100A9 Protein Complex Mediates Psoriasis by Regulating the Expression of Complement Factor C3

Schönthaler, Helia B.; Guinea-Viniegra, Juan; Wculek, Stefanie K.; Ruppen, Isabel; Ximénez-Embún, Pilar; Guío-Carrión, Ana; Navarro, R.; Hogg, Nancy; Ashman, Keith; Wagner, Erwin F.

doi:10.1016/j.immuni.2013.11.011

Cited by 215 publications

(233 citation statements)

References 49 publications

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“…The S100A8/A9 complex (also known as calprotectin) was shown to be constitutively expressed in monocytes in various tissues associated with inflammatory processes while weakly expressed in tissue macrophages (35)(36)(37)(38). The expression of this complex was shown to be regulated by lipopolysaccharide (LPS) (39). This result was consistent with our proteomics analysis results (Figs.…”

Section: Analysis Of Protein Expression In Differentiated Monocytes-supporting

confidence: 90%

Quantitative Proteomics Reveals a Role for Epigenetic Reprogramming During Human Monocyte Differentiation

Nicholas

Tang²,

Zhang

et al. 2015

Molecular & Cellular Proteomics

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The differentiation of monocytes into macrophages and dendritic cells involves mechanisms for activation of the innate immune system in response to inflammatory stimuli, such as pathogen infection and environmental cues. Epigenetic reprogramming is thought to play an important role during monocyte differentiation. Complementary to cell surface markers, the characterization of monocytic cell lineages by mass spectrometry based protein/histone expression profiling opens a new avenue for studying immune cell differentiation. Here, we report the application of mass spectrometry and bioinformatics to identify changes in human monocytes during their differentiation into macrophages and dendritic cells. Our data show that linker histone H1 proteins are significantly down-regulated during monocyte differentiation. Although highly enriched H3K9-methyl/S10-phos/K14-acetyl tri-modification forms of histone H3 were identified in monocytes and macrophages, they were dramatically reduced in dendritic cells. In contrast, histone H4 K16 acetylation was found to be markedly higher in dendritic cells than in monocytes and macrophages. We also found that global hyperacetylation generated by the nonspecific histone deacetylase HDAC inhibitor Apicidin induces monocyte differentiation. Together, our data suggest that specific regulation of inter-and intra-histone modifications including H3 K9 methylation, H3 S10 phosphorylation, H3 K14 acetylation, and H4 K16 acetylation must occur in concert with chromatin remodeling by linker histones for cell cycle progression and differentiation of human myeloid cells into macrophages and dendritic cells. Molecular & Cellular

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Section: Analysis Of Protein Expression In Differentiated Monocytes-supporting

confidence: 90%

Quantitative Proteomics Reveals a Role for Epigenetic Reprogramming During Human Monocyte Differentiation

Nicholas

Tang²,

Zhang

et al. 2015

Molecular & Cellular Proteomics

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“…Enhanced expression of the calcium-binding proteins S100 calcium-binding protein A8 and A9 (S100A8 and S100A9) was observed in human prostate cancer, 20 and Jun/AP-1 controls the S100a8/S100a9 expression in mouse epidermis. 21,22 Increased expression of S100A8 and S100A9 was detected by western blot and IHC in JunB ΔP ; Pten ΔP tumours, while mRNA expression was unchanged (Figure 4a and c). The S100A8-and S100A9-positive cells appeared to be non-epithelial and IHC co-staining with F4/80 indicated that most positive cells were of the monocyte/ macrophage lineage (Figure 4b, Supplementary Figure 4a).…”

Section: Resultsmentioning

confidence: 97%

Loss of JUNB/AP-1 promotes invasive prostate cancer

et al. 2014

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Prostate cancer is a frequent cause of male death in the Western world. Relatively few genetic alterations have been identified, likely owing to disease heterogeneity. Here, we show that the transcription factor JUNB/AP-1 limits prostate cancer progression. JUNB expression is increased in low-grade prostate cancer compared with normal human prostate, but downregulated in highgrade samples and further decreased in all metastatic samples. To model the hypothesis that this downregulation is functionally significant, we genetically inactivated Junb in the prostate epithelium of mice. When combined with Pten (phosphatase and tensin homologue) loss, double-mutant mice were prone to invasive cancer development. Importantly, invasive tumours also developed when Junb and Pten were inactivated in a small cell population of the adult anterior prostate by topical Cre recombinase delivery. The resulting tumours displayed strong histological similarity with human prostate cancer. Loss of JunB expression led to increased proliferation and decreased senescence, likely owing to decreased p16Ink4a and p21 CIP1 in epithelial cells. Furthermore, the tumour stroma was altered with increased osteopontin and S100 calcium-binding protein A8/9 expression, which correlated with poor prognoses in patients. These data demonstrate that JUNB/AP-1 cooperates with PTEN signalling as barriers to invasive prostate cancer, whose concomitant genetic or epigenetic suppression induce malignant progression.

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“…[25][26][27][28] As a general principle, extracellular S100A9 stimulates innate immune cells and endothelial cells, via interactions with the receptor for advanced glycation end products 29 and Toll-like receptor-4 (TLR4), 30 to elicit and augment proinflammatory responses; however, its expression in granulomas as well as its role in granuloma formation have never been addressed. In the present study, we found that neutrophils expressing S100A9 accumulated in the central area of granulomas, and that the S100A9 protein may serve as a key molecule for granuloma formation.…”

Section: Discussionmentioning

confidence: 99%

Neutrophils and the S100A9 protein critically regulate granuloma formation

et al. 2016

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Key Points• S100A91 neutrophils accumulated prominently in the central area of granulomas in humans and guinea pigs.• Granuloma formation was markedly impaired by a treatment with the S100A9 inhibitor, tasquinimod. antigen as S100A9, a calcium-binding protein of the S100 family, which was expressed abundantly in neutrophils. Consistent with the multifaceted functions attributed to S100A9, including its role in neutrophil extravasation and macrophage activation, the blockade of S100A9 functions with the specific inhibitor, tasquinimod, impaired the formation of organized granulomas with neutrophil cores. These results demonstrate the critical role of neutrophils and the S100A9 protein in granuloma formation. Because intragranuloma S100A9 1 neutrophils were also detected in humans, these results indicate the potential of tasquinimod, a new anticancer drug candidate, for manipulating human granulomatous diseases.

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S100A8-S100A9 Protein Complex Mediates Psoriasis by Regulating the Expression of Complement Factor C3

Cited by 215 publications

References 49 publications

Quantitative Proteomics Reveals a Role for Epigenetic Reprogramming During Human Monocyte Differentiation

Quantitative Proteomics Reveals a Role for Epigenetic Reprogramming During Human Monocyte Differentiation

Loss of JUNB/AP-1 promotes invasive prostate cancer

Neutrophils and the S100A9 protein critically regulate granuloma formation

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