S100A12 Expression Is Modulated During Monocyte Differentiation and Reflects Periodontitis Severity

Lira-Júnior, Ronaldo; Holmström, Sofia Björnfot; Clark, Reuben; Zwicker, Stephanie; Majster, Mirjam; Johannsen, Gunnar; Axtelius, Björn; Åkerman, Sigvard; Svensson, Mattias; Klinge, Björn; Boström, Elisabeth A.

doi:10.3389/fimmu.2020.00086

Cited by 39 publications

(29 citation statements)

References 40 publications

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“…This Previous studies found that S100A12 has different functions including chemotactic activity, inflammatory reaction, oxidative stress, and activation of intracellular signaling cascades. Mounting evidence clarified that S100A12 is elevated and involved in several inflammatory diseases, such as inflammatory bowel disease, rheumatoid arthritis, juvenile idiopathic arthritis, cystic fibrosis, and periodontitis (18)(19)(20)(21). According to recently published studies, S100A12 has been implicated in the process of many pulmonary inflammatory diseases (22)(23)(24)(25)(26)(27).…”

Section: Discussionmentioning

confidence: 99%

“…Increasing evidences have demonstrated that the counts of immune cells, such as B cells, T cells, and NK cells, were strongly correlated with the severity in CAP patients (15)(16)(17). Previous studies suggested that an increase of S100A12 is associated with several inflammatory diseases, such as inflammatory bowel disease, rheumatoid arthritis, juvenile idiopathic arthritis, cystic fibrosis, and periodontitis (18)(19)(20)(21). Moreover, recent researches indicated that S100A12 can be implicated in idiopathic pulmonary fibrosis, acute lung injury, pulmonary hypertension, interstitial lung disease, and acute respiratory distress syndrome (22)(23)(24)(25)(26)(27).…”

Section: Introductionmentioning

confidence: 99%

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Associations of Serum S100A12 With Severity and Prognosis in Patients With Community-Acquired Pneumonia: A Prospective Cohort Study

et al. 2021

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BackgroundPrevious studies indicated the calcium-binding protein S100A12 to be involved in the pathophysiology of pulmonary inflammatory diseases. However, the role of S100A12 has remained elusive in patients with community-acquired pneumonia (CAP). Therefore, the purpose of this prospective cohort study was to evaluate the association between serum S100A12 with severity and prognosis in CAP patients.MethodsTwo groups with either 239 CAP patients or 239 healthy controls were enrolled in our study. Fasting blood and clinical characteristics were collected. On admission, serum S100A12 was measured using enzyme-linked immunosorbent assay (ELISA).ResultsSerum S100A12 was increased in CAP patients compared to control subjects. Furthermore, serum S100A12 was elevated according to the severity of CAP. Correlative analysis suggested that the level of serum S100A12 was associated with blood routine indices, renal function markers, inflammatory cytokines and other clinical parameters among CAP patients. Additionally, linear and logistical regression analyses indicated that serum S100A12 was positively associated with CAP severity scores in CAP patients. In addition, the association of high serum S100A12 and prognosis was accessed using a follow-up research. Elevated serum S100A12 on admission increased the risk of death and hospital stay in CAP patients during hospitalization.ConclusionsElevated serum S100A12 on admission is positively associated with the severity and adverse prognosis in CAP patients, suggesting that S100A12 may involve in the pathophysiological process of CAP. The titre of serum S100A12 may be used as a biomarker for diagnosis and prognosis among CAP patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Associations of Serum S100A12 With Severity and Prognosis in Patients With Community-Acquired Pneumonia: A Prospective Cohort Study

et al. 2021

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“…Previous studies have generated immune oral gingival models by incorporating primary monocytes, peripheral blood mononuclear cells, or myeloid cancer cell lines (MonoMac-6 [MM6], U937, or THP-1 cells) and by observing changes in inflammatory markers and proteases in response to bacterial LPS, [18][19][20][21] bacterial biofilms, 22 or X-ray treatment. 23 While the use of myeloid cancer cell lines presents fewer technical limitations and reproducibility compared with primary immune cells, there is good evidence that their phenotype and function is markedly altered compared with primary cells, with the often used THP-1 cells shown to express aberrant levels of key macrophage phenotypic markers and thus respond differently to stimuli.…”

Section: Introductionmentioning

confidence: 99%

Immunoresponsive Tissue-Engineered Oral Mucosal Equivalents Containing Macrophages

Ollington

Colley

2021

Tissue Engineering Part C: Methods

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Macrophages play a key role in orchestrating the host immune response toward invading organisms or non-self molecules in the oral mucosa. Three-dimensional (3D) oral mucosal equivalents (OME) containing oral fibroblasts and keratinocytes are used extensively to mimic the human oral mucosa where they have been employed to examine innate immune responses to both bacterial and fungal pathogens as well as to biomaterials. Although the presence of immune cells is critical in generating an immune response, very few studies have incorporated leukocytes into OME, and to date, none have contained primary human macrophages. In this study, we report the generation of an immunocompetent OME to investigate immune responses toward bacterial challenge. Primary human monocyte-derived macrophages (MDM) were as responsive to bacterial lipopolysaccharide (LPS) challenge when cultured within a 3D hydrogel in terms of proinflammatory cytokine (IL-6, CXCL8, and TNF-α) gene expression and protein secretion compared with culture as two-dimensional monolayers. MDM were incorporated into a type 1 collagen hydrogel along with oral fibroblasts and the apical surface seeded with oral keratinocytes to generate an MDM-containing OME. Full-thickness MDM-OME displayed a stratified squamous epithelium and a fibroblast-populated connective tissue containing CD68-positive MDM that could be readily isolated to a single-cell population for further analysis by collagenase treatment followed by flow cytometry. When stimulated with LPS, MDM-OME responded with increased proinflammatory cytokine secretion, most notably for TNF-α that increased 12-fold when compared with OME alone. Moreover, this proinflammatory response was inhibited by pretreatment with dexamethasone, showing that MDM-OME are also amenable to drug treatment. Dual-labeled immunofluorescence confocal microscopy revealed that MDM were the sole source of TNF-α production within MDM-OME. These data show functional activity of MDM-OME and illustrate their usefulness for investigations aimed at monitoring the immune response of the oral mucosa to pathogens, biomaterials, and for tissue toxicity and anti-inflammatory drug delivery studies. Impact statement Three-dimensional in vitro models of the oral mucosa have been used extensively to investigate the host response to pathogens, but, to date, few have contained primary leukocytes. In this report, we describe the successful incorporation of primary human macrophages into oral mucosal equivalents (OME). These macrophage-containing models were histologically similar to the oral mucosa and immunoresponsive to bacterial lipopolysaccharides by upregulation of key proinflammatory markers. These advanced OME will significantly aid research into host–pathogen interaction, biomaterial toxicity, and drug delivery studies where the presence of an immune cell component is critical to better represent host oral tissue.

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“…9 The stimulation by other inflammatory mediators can change the protein conformation of S100A12, thereby exposing the binding site of target protein, which can interact with specific proteins or peptides to play biological functions. 10 These calciumbinding proteins control critical cellular pathways such as cytoskeleton, cell migration and adhesion, active oxidative defense, wound healing, activation of inflammatory cells, chemotaxis, and antimicrobial effects, which are also involved in the pathophysiological process of metabolic and neoplastic diseases. 11 So, we considered that S100A12 may regulate inflammation factors to prevent osteoarthritis.…”

Section: Introductionmentioning

confidence: 99%

Clinical severity of serum S100A12 levels in patients with osteoarthritis and S100A12 open inflammation of osteoarthritis model by NLRP3

Zhai

Sun

et al. 2021

Eur J Inflamm

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Osteoarthritis is a common chronic bone and joint disease, which is characterized by degenerative changes and destruction of articular cartilage, secondary hyperostosis. This study aimed to investigate the clinical severity and mechanism of S100A12 in patients with osteoarthritis. Serum samples were obtained from patients with osteoarthritis or normal volunteer in Minhang Branch of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine affiliated to Shanghai University of Traditional Chinese Medicine (Shanghai, China). C57BL/6J mice performed Resection of the medial collateral ligament and medial meniscus as mice model. MC3T3-E1 cells were induced with 100 ng of LPS as vitro model. The serum level of S100A12 was increased in patients with osteoarthritis. Similarly, S100A12 levels of serum and bone tissue from mice model of osteoarthritis were also higher than those of sham group. Over-expression of S100A12 promoted inflammation levels while down-regulation of S100A12 decreased inflammation levels in in vitro model of osteoarthritis. NLRP3 is an important target of S100A12 in pro-inflammation effects of osteoarthritis. NLRP3 was involved in the effects of S100A12 on inflammation in in vitro model of osteoarthritis. S100A12 also accelerated inflammation by NLRP3 in mice model of osteoarthritis. We conclude that serum S100A12 levels was a possible clinical severity, open inflammation of osteoarthritis model by NLRP3 and its receptors may be effective in preventing the development of osteoarthritis.

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S100A12 Expression Is Modulated During Monocyte Differentiation and Reflects Periodontitis Severity

Cited by 39 publications

References 40 publications

Associations of Serum S100A12 With Severity and Prognosis in Patients With Community-Acquired Pneumonia: A Prospective Cohort Study

Associations of Serum S100A12 With Severity and Prognosis in Patients With Community-Acquired Pneumonia: A Prospective Cohort Study

Immunoresponsive Tissue-Engineered Oral Mucosal Equivalents Containing Macrophages

Clinical severity of serum S100A12 levels in patients with osteoarthritis and S100A12 open inflammation of osteoarthritis model by NLRP3

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