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Guus P Leijte, Hettie Custers, Jelle Gerretsen, Amon Heijne, Johannes Roth, Thomas Vogl, Gert J Scheffer, Peter Pickkers, Matthijs Kox
Introduction: Danger-associated molecular patterns (DAMPs) can elicit immune responses and may subsequently induce an immune-suppressed state. Previous work showed that increased plasma levels of DAMPs are associated with immune suppression and increased susceptibility toward infections in trauma patients. Like trauma, major surgical procedures, such as cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC), are also thought to cause profound DAMP release...
2018: Frontiers in Immunology
Igor A Iashchishyn, Marina Gruden, Roman Moskalenko, Tatiana Davydova, Chao Wang, Robert D E Sewell, Ludmilla A Morozova-Roche
Amyloid formation and neuroinflammation are major features of Alzheimer's disease pathology. Proinflammatory mediator S100A9 was shown to act as a link between the amyloid and neuroin-flammatory cascades in Alzheimer's disease, leading together with Aβ to plaque formation, neu-ronal loss and memory impairment. In order to examine if S100A9 alone in its native and amy-loid states can induce neuronal stress and memory impairment, we have administered S100A9 species intranasally to aged mice. Single and sequential immunohistochemistry and passive avoidance behavioral test were conducted to evaluate the consequences...
April 4, 2018: ACS Chemical Neuroscience
Rui Wu, Yuhong Zhang, Yu Xiang, Yishu Tang, Fang Cui, Ju Cao, Lan Zhou, Yan You, Liang Duan
BACKGROUND: S100A9 protein, which is recently classified as a novel damage associated molecular pattern, is released from stressed cells undergoing necrosis or secreted by living cells undergoing a stress that act as endogenous danger signal associated with infection, tissue damage and cancer. Here, we evaluated the relationship of serum S100A9 with viral replication and liver necroinflammation in patients with chronic hepatitis B (CHB) infection. METHODS: A total of one hundred and eighty-three recruited patients with CHB infection underwent liver biopsy for grading of necroinflammation (G) and staging of fibrosis (S)...
April 3, 2018: Journal of Translational Medicine
Thomas Vogl, Athanasios Stratis, Viktor Wixler, Tom Völler, Sumita Thurainayagam, Selina K Jorch, Stefanie Zenker, Alena Dreiling, Deblina Chakraborty, Mareike Fröhling, Peter Paruzel, Corinna Wehmeyer, Sven Hermann, Olympia Papantonopoulou, Christiane Geyer, Karin Loser, Michael Schäfers, Stephan Ludwig, Monika Stoll, Tomas Leanderson, Joachim L Schultze, Simone König, Thomas Pap, Johannes Roth
Autoimmune diseases, such as psoriasis and arthritis, show a patchy distribution of inflammation despite systemic dysregulation of adaptive immunity. Thus, additional tissue-derived signals, such as danger-associated molecular patterns (DAMPs), are indispensable for manifestation of local inflammation. S100A8/S100A9 complexes are the most abundant DAMPs in many autoimmune diseases. However, regulatory mechanisms locally restricting DAMP activities are barely understood. We now unravel for the first time, to our knowledge, a mechanism of autoinhibition in mice and humans restricting S100-DAMP activity to local sites of inflammation...
April 3, 2018: Journal of Clinical Investigation
Mariaimmacolata Preianò, Giuseppina Maggisano, Maria Stella Murfuni, Chiara Villella, Corrado Pelaia, Tiziana Montalcini, Nicola Lombardo, Girolamo Pelaia, Rocco Savino, Rosa Terracciano
PURPOSE: Gingival crevicular fluid (GCF) is an important diagnostic source of biomarkers for both periodontitis and gingivitis. However, GCF peptide signature may change depending by factors such as handling and storage. Here we propose a standardized methodology for GCF analysis by MALDI-TOF/TOF-MS in order to distinguish a characteristic peptide signature of gingivitis. EXPERIMENTAL DESIGN: We determined the best storage/handling conditions which may ensure the stability of the endogenous peptidome in GCF and then we performed MALDI-TOF MS comparative analysis...
March 30, 2018: Proteomics. Clinical Applications
Véronique Schenten, Sébastien Plançon, Nicolas Jung, Justine Hann, Jean-Luc Bueb, Sabrina Bréchard, Eric J Tschirhart, Fabrice Tolle
S100A8 and S100A9 are members of the S100 family of cytoplasmic EF-hand Ca2+ -binding proteins and are abundantly expressed in the cytosol of neutrophils. In addition to their intracellular roles, S100A8/A9 can be secreted in the extracellular environment and are considered as alarmins able to amplify the inflammatory response. The intracellular activity of S100A8/A9 was shown to be regulated by S100A9 phosphorylation, but the importance of this phosphorylation on the extracellular activity of S100A8/A9 has not yet been extensively studied...
2018: Frontiers in Immunology
Julie Cremniter, Charles Bodet, David Tougeron, Xavier Dray, Joëlle Guilhot, Jean-François Jégou, Franck Morel, Jean-Claude Lecron, Christine Silvain, Christophe Burucoa
BACKGROUND: The pathological determinism of H. pylori infection is explained by complex interplay between bacterial virulence and host inflammatory response. In a large prospective multicenter clinical study, Th17 response, expression of antimicrobial peptides (AMPs), cagA and vacA status, and bacterial density were investigated in the gastric mucosa of H. pylori -infected patients. MATERIALS AND METHODS: Gastric inflammatory response was analyzed by RT-qPCR for quantification of Th17 cytokines (IL-17A, IL-22), CXCL-8, and AMPs (BD2 and S100A9) mRNA levels in gastric biopsies...
March 27, 2018: Helicobacter
Koji Naruishi, Toshihiko Nagata
Periodontitis is a bacterial infectious disease, and many inflammatory cytokines regulate periodontitis pathophysiology through a crosstalk between tissue cells and immune cells. Interleukin (IL)-6 is an important cytokine involved in the regulation of host response to bacterial infection. Human Gingival Fibroblasts (HGFs) are the most abundant cells in gingival connective tissues. Various HGF responses to periodontal pathogens or inflammatory cytokines contribute to the development of periodontitis. Lipopolysaccharide derived from Porphyromonas gingivalis (Pg LPS) and IL-1β significantly increase IL-6 production in HGFs...
March 25, 2018: Journal of Cellular Physiology
Hanne Hauger, Christian Ritz, Charlotte Mortensen, Christian Mølgaard, Stine Broeng Metzdorff, Hanne Frøkiær, Camilla Trab Damsgaard
PURPOSE: We explored the effect of winter cholecalciferol (vitamin D3 ) supplementation on innate immune markers in healthy Danish children (55°N). METHODS: In the double-blind, placebo-controlled trial, ODIN Junior, 119 healthy, white, 4-8 year-olds were randomized to 0 (placebo), 10 or 20 µg/day of vitamin D3 for 20 weeks (October-March). Cheek mucosal swabs, blood samples, and questionnaires on acute respiratory infections the previous month were collected at baseline and endpoint...
March 23, 2018: European Journal of Nutrition
Maurizio Baldassarre, Cesare M Baronio, Ludmilla A Morozova-Roche, Andreas Barth
Two main amyloid-β peptides of different length (Aβ40 and Aβ42 ) are involved in Alzheimer's disease. Their relative abundance is decisive for the severity of the disease and mixed oligomers may contribute to the toxic species. However, little is know about the extent of mixing. To study whether Aβ40 and Aβ42 co-aggregate, we used Fourier transform infrared spectroscopy in combination with13 C-labeling and spectrum calculation and focused on the amide I vibration, which is sensitive to backbone structure...
December 1, 2017: Chemical Science
Apurva Atak, Samiksha Khurana, Kishore Gollapalli, Panga Jaipal Reddy, Roei Levy, Stav Ben-Salmon, Dror Hollander, Maya Donyo, Anke Heit, Agnes Hotz-Wagenblatt, Hadas Biran, Roded Sharan, Shailendra Rane, Ashutosh Shelar, Gil Ast, Sanjeeva Srivastava
Adenocarcinomas are cancers originating from the gland forming cells of the colon and rectal lining, and are known to be the most common type of colorectal cancers. The current diagnosis strategies for colorectal cancers include biopsy, laboratory tests, and colonoscopy which are time consuming. Identification of protein biomarkers could aid in the detection of colon adenocarcinomas (CACs). In this study, tissue proteome of colon adenocarcinomas ( n = 11) was compared with the matched control specimens ( n = 11) using isobaric tags for relative and absolute quantitation (iTRAQ) based liquid chromatography-mass spectrometry (LC-MS/MS) approach...
March 2, 2018: Oncotarget
Marta Podgórska, Monika Ołdak, Anna Marthaler, Alina Fingerle, Barbara Walch-Rückheim, Stefan Lohse, Cornelia S L Müller, Thomas Vogt, Mart Ustav, Artur Wnorowski, Magdalena Malejczyk, Sławomir Majewski, Sigrun Smola
Persistent genus β-HPV (human papillomavirus) infection is a major co-factor for non-melanoma skin cancer in patients suffering from the inherited skin disease epidermodysplasia verruciformis (EV). Malignant EV lesions are particularly associated with HPV type 5 or 8. There is clinical and molecular evidence that HPV8 actively suppresses epithelial immunosurveillance by interfering with the recruitment of Langerhans cells, which may favor viral persistence. Mechanisms how persistent HPV8 infection promotes the carcinogenic process are, however, less well understood...
2018: Frontiers in Microbiology
Scott J Denstaedt, Joanna L Spencer-Segal, Michael W Newstead, Klaudia Laborc, Anne P Zhao, Alexander Hjelmaas, Xianying Zeng, Huda Akil, Theodore J Standiford, Benjamin H Singer
Sepsis commonly results in acute and chronic brain dysfunction, which dramatically increases the morbidity associated with this common disease. Chronic brain dysfunction in animal models of sepsis survival is linked to persistent neuroinflammation and expression of multiple cytokines. However, we have found previously that microglia predominantly upregulate the damage associated molecule S100A8/A9 after sepsis. In this article, we show that S100A8/A9 is increased in the brains of patients who died of sepsis and that S100A8 is expressed in astrocytes and myeloid cells...
March 21, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Chinthalapally V Rao
In recent times, bitter melon extract (BME) has gained significant attention for its anticancer efficacy against various malignancies. In this issue, Sur and colleagues show that BME prevents the development of 4-nitronitroquinoline 1-oxide-induced oral dysplasia and squamous cell carcinoma (SCC) in an immunocompetent mouse model. Importantly, gene ontology and pathway analyses revealed an elevated expression of s100a9, IL23a, IL1β, and PDCD1/PD1 of immune system during oral cancer development, which was significantly suppressed by BME...
March 20, 2018: Cancer Prevention Research
Ester Lozano, Tania Díaz, Mari-Pau Mena, Guillermo Suñe, Xavier Calvo, Marcos Calderón, Lorena Pérez-Amill, Vanina Rodríguez, Patricia Pérez-Galán, Gaël Roué, M Teresa Cibeira, Laura Rosiñol, Ignacio Isola, Luis-Gerardo Rodríguez-Lobato, Beatriz Martin-Antonio, Joan Bladé, Carlos Fernández de Larrea
Mechanisms of immune regulation may control proliferation of aberrant plasma cells (PCs) in patients with monoclonal gammopathy of undetermined significance (MGUS) preventing progression to active multiple myeloma (MM). We hypothesized that CD85j ( LILRB1 ), an inhibitory immune checkpoint for B cell function, may play a role in MM pathogenesis. In this study, we report that patients with active MM had significantly lower levels of CD85j and its ligand S100A9. Decreased CD85j expression could also be detected in the premalignant condition MGUS, suggesting that loss of CD85j may be an early event promoting tumor immune escape...
March 12, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Andrea N Loes, Jamie T Bridgham, Michael J Harms
Toll-like receptor 4 (TLR4) induces inflammation in response to both pathogen- and host-derived molecules. Lipopolysaccharide (LPS) recognition by TLR4 has been shown to occur across the amniotes, but endogenous signaling through TLR4 has not been validated outside of placental mammals. To determine whether endogenous danger signaling is also shared across amniotes, we studied the evolution of TLR4-activation by the calgranulin proteins (S100A8, S100A9, and S100A12), a clade of host molecules that potently activate TLR4 in placental mammals...
2018: Frontiers in Immunology
Boya Zhang, Xianzhen Chen, Qiang Zhou, Yinjing Song, Siyuan Sun, Hao Cheng
OBJECTIVE: Human papillomavirus (HPV) is the most common sexually transmitted agent in the world. HPV6b is a low-risk type of HPVs that causes benign verrucous hyperplastic lesions of the skin and anal genital mucosa. Previous research has indicated that HPV genotype 6 is sometimes associated with high-grade lesions and anal cancer. The pathogenesis of low-risk HPV infection and its relationship to high-risk HPV is not clear at present. The E7 protein, which is encoded by HPV early -expressing genes, plays an important role in HPV infection...
March 1, 2018: Gene
Vinay V Kumar, Bonney L James, Manuela Ruß, Stefan Mikkat, Amritha Suresh, Peer W Kämmerer, Michael O Glocker
AIM: The aim of this study was to determine whether intra-oral de novo regenerated mucosa (D) that grew over free fibula flap reconstructed-mandibles resembled the donor tissue i.e. external skin (S) of the lateral leg, or the recipient site tissue, i.e. keratinized oral mucosa (K). MATERIALS AND METHODS: Differential proteome analysis was performed with ten tissue samples from each of the three groups: de novo regenerated mucosa (D), external skin (S), and keratinized oral mucosa (K)...
March 2018: Oral Oncology
Andrea Olmos-Ortiz, Janice García-Quiroz, Euclides Avila, Felipe Caldiño-Soto, Ali Halhali, Fernando Larrea, Lorenza Díaz
PROBLEM: Calcitriol, the hormonal form of vitamin D3 (VD), stimulates placental antimicrobial peptides expression; nonetheless, the regulation of calcitriol biosynthesis in the presence of bacterial products and its consequence on placental innate immunity have scarcely been addressed. METHOD OF STUDY: We investigated how some bacterial products modify placental VD metabolism and its ability to induce antimicrobial peptides gene expression. RESULTS: Cultured human trophoblasts biosynthesized calcitriol only in the presence of its precursor calcidiol, a process that was inhibited by cyclic-AMP but stimulated by lipopolysaccharide (LPS)...
March 1, 2018: American Journal of Reproductive Immunology: AJRI
Po-Hao Feng, Chih-Teng Yu, Kuan-Yuan Chen, Ching-Shan Luo, Shen Ming Wu, Chien-Ying Liu, Lu Wei Kuo, Yao-Fei Chan, Tzu-Tao Chen, Chih-Cheng Chang, Chun-Nin Lee, Hsiao-Chi Chuang, Chiou-Feng Lin, Chia-Li Han, Wei-Hwa Lee, Kang-Yun Lee
Background: Monocytic myeloid-derived suppressor cells (MDSCs), particularly the S100A9+ subset, has been shown initial clinical relevance. However, its role in EGFR-mutated lung adenocarcinoma, especially to EGFR-tyrosine kinase inhibitor (EGFR-TKI) is not clear. In a clinical setting of EGFR mutated lung adenocarcinoma, a role of the MDSC apart from T cell suppression was also investigated. Results: Blood monocytic S100A9+ MDSC counts were higher in lung cancer patients than healthy donors, and were associated with poor treatment response and shorter progression-free survival (PFS)...
January 26, 2018: Oncotarget
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