scholarly journals Regulation of Osteoblast Differentiation by Cytokine Networks

2021 ◽  
Vol 22 (6) ◽  
pp. 2851
Author(s):  
Dulshara Sachini Amarasekara ◽  
Sumi Kim ◽  
Jaerang Rho
Keyword(s):  
Transcription Factor ◽  
Osteoblast Differentiation ◽  
Interleukin 10 ◽  
Interferon Γ ◽  
The Body ◽  
Oncostatin M ◽  
Bone Modeling ◽  
Activator Protein 1 ◽  
Cytokine Networks ◽  
Factor Α

Osteoblasts, which are bone-forming cells, play pivotal roles in bone modeling and remodeling. Osteoblast differentiation, also known as osteoblastogenesis, is orchestrated by transcription factors, such as runt-related transcription factor 1/2, osterix, activating transcription factor 4, special AT-rich sequence-binding protein 2 and activator protein-1. Osteoblastogenesis is regulated by a network of cytokines under physiological and pathophysiological conditions. Osteoblastogenic cytokines, such as interleukin-10 (IL-10), IL-11, IL-18, interferon-γ (IFN-γ), cardiotrophin-1 and oncostatin M, promote osteoblastogenesis, whereas anti-osteoblastogenic cytokines, such as tumor necrosis factor-α (TNF-α), TNF-β, IL-1α, IL-4, IL-7, IL-12, IL-13, IL-23, IFN-α, IFN-β, leukemia inhibitory factor, cardiotrophin-like cytokine, and ciliary neurotrophic factor, downregulate osteoblastogenesis. Although there are gaps in the body of knowledge regarding the interplay of cytokine networks in osteoblastogenesis, cytokines appear to be potential therapeutic targets in bone-related diseases. Thus, in this study, we review and discuss our osteoblast, osteoblast differentiation, osteoblastogenesis, cytokines, signaling pathway of cytokine networks in osteoblastogenesis.

Localized pancreatic NF-κB activation and inflammatory response in taurocholate-induced pancreatitis

2001 ◽  
Vol 280 (6) ◽  
pp. G1197-G1208 ◽  
Author(s):  
Eva Vaquero ◽  
Ilya Gukovsky ◽  
Vjekoslav Zaninovic ◽  
Anna S. Gukovskaya ◽  
Stephen J. Pandol
Keyword(s):  
Transcription Factor ◽  
Inflammatory Response ◽  
Pancreatic Head ◽  
Pancreatic Injury ◽  
Nuclear Factor Κb ◽  
Saline Infusion ◽  
Activator Protein 1 ◽  
Local Inflammatory Response ◽  
Monocyte Chemoattractant Protein 1 ◽  
Factor Α

Transcription factor nuclear factor-κB (NF-κB) is activated in cerulein pancreatitis and mediates cytokine expression. The role of transcription factor activation in other models of pancreatitis has not been established. Here we report upregulation of NF-κB and inflammatory molecules, and their correlation with local pancreatic injury, in a model of severe pancreatitis. Rats received intraductal infusion of taurocholate or saline, and the pancreatic head and tail were analyzed separately. NF-κB and activator protein-1 (AP-1) activation were assessed by gel shift assay, and mRNA expression of interleukin-6, tumor necrosis factor-α, KC, monocyte chemoattractant protein-1, and inducible nitric oxide synthase was assessed by semiquantitative RT-PCR. Morphological damage and trypsin activation were much greater in the pancreatic head than tail, in parallel with a stronger activation of NF-κB and cytokine mRNA. Saline infusion mildly affected these parameters. AP-1 was strongly activated in both pancreatic segments after either taurocholate or saline infusion. NF-κB inhibition with N-acetylcysteine ameliorated the local inflammatory response. Correlation between localized NF-κB activation, cytokine upregulation, and tissue damage suggests a key role for NF-κB in the development of the inflammatory response of acute pancreatitis.

scholarly journals HIF1α/TET1 Pathway Mediates Hypoxia-Induced Adipocytokine Promoter Hypomethylation in Human Adipocytes

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 134 ◽  
Author(s):  
Mohamed M. Ali ◽  
Shane A. Phillips ◽  
Abeer M. Mahmoud
Keyword(s):  
Dna Methylation ◽  
Interleukin 1 ◽  
Hypoxia Inducible Factor ◽  
Interferon Γ ◽  
The Body ◽  
Human Adipocytes ◽  
Protein Levels ◽  
Factor Α ◽  
Necrosis Factor

Obesity is associated with the accumulation of dysfunctional adipose tissue that secretes several pro-inflammatory cytokines (adipocytokines). Recent studies have presented evidence that adipose tissues in obese individuals and animal models are hypoxic, which may result in upregulation and stabilization of the hypoxia inducible factor HIF1α. Epigenetic mechanisms such as DNA methylation enable the body to respond to microenvironmental changes such as hypoxia and may represent a mechanistic link between obesity-associated hypoxia and upregulated inflammatory adipocytokines. The purpose of this study was to investigate the role of hypoxia in modifying adipocytokine DNA methylation and subsequently adipocytokine expression. We suggested that this mechanism is mediated via the DNA demethylase, ten-eleven translocation-1 (TET1), transcription of which has been shown to be induced by HIF1α. To this end, we studied the effect of hypoxia (2% O2) in differentiated subcutaneous human adipocytes in the presence or absence of HIF1α stabilizer (Dimethyloxalylglycine (DMOG), 500 μM), HIF1α inhibitor (methyl 3-[[2-[4-(2-adamantyl) phenoxy] acetyl] amino]-4-hydroxybenzoate, 30 μM), or TET1-specific siRNA. Subjecting the adipocytes to hypoxia significantly induced HIF1α and TET1 protein levels. Moreover, hypoxia induced global hydroxymethylation, reduced adipocytokine DNA promoter methylation, and induced adipocytokine expression. These effects were abolished by either HIF1α inhibitor or TET1 gene silencing. The major hypoxia-responsive adipocytokines were leptin, interleukin-1 (IL6), IL1β, tumor necrosis factor α (TNFα), and interferon γ (IFNγ). Overall, these data demonstrate an activation of the hydroxymethylation pathway mediated by TET1. This pathway contributes to promoter hypomethylation and gene upregulation of the inflammatory adipocytokines in adipocytes in response to hypoxia.

Soluble LILRA3, a Potential Natural Antiinflammatory Protein, Is Increased in Patients with Rheumatoid Arthritis and Is Tightly Regulated by Interleukin 10, Tumor Necrosis Factor-α, and Interferon-γ

2010 ◽  
Vol 37 (8) ◽  
pp. 1596-1606 ◽  
Author(s):  
HONGYAN AN ◽  
VASUDHA CHANDRA ◽  
BARBARA PIRAINO ◽  
LUIS BORGES ◽  
CAROLYN GECZY ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Synovial Fluid ◽  
Protein Expression ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Interleukin 10 ◽  
Interferon Γ ◽  
Factor Α ◽  
Necrosis Factor

Objective.Leukocyte immunoglobulin-like receptor A3 (LILRA3) belongs to a family of cell-surface receptors with inhibitory or activating functions. LILRA3 lacks transmembrane and cytoplasmic domains, suggesting that it may be secreted. LILRA3 has high homology to activating LILRA1 and A2, hence may act as a soluble agonist/antagonist to these receptors. Individuals lacking the LILRA3 gene have higher incidence of multiple sclerosis and Sjögren’s syndrome, suggesting LILRA3 may be antiinflammatory. LILRA3 mRNA was detected in monocytes and mast cells but no protein expression has ever been described. Our aim was to examine LILRA3 protein expression in serum and synovial fluid of patients with rheumatoid arthritis (RA) and determine its in vitro regulation.Methods.We developed a new ELISA to examine levels of LILRA3 in serum, synovial fluid, and/or culture supernatants from controls and patients with RA, degenerative arthritis, or gout. We used qRT-PCR and flow cytometry to determine the expression and cytokine-mediated regulation of LILRA3.Results.LILRA3 protein is constitutively present in normal serum, with significantly higher concentrations in patients with RA. Serum LILRA3 concentrations from RA patients correlated with disease activity and levels in synovial fluid. Treatment of monocytes with interleukin 10 or interferon-γ significantly upregulated while tumor necrosis factor-α significantly downregulated LILRA3 mRNA and protein expression.Conclusion.We show for the first time that LILRA3 is significantly increased in serum of patients with RA and is tightly regulated by key cytokines involved in pathogenesis of RA. These results suggest that LILRA3 may play a role in chronic inflammatory conditions such as RA.

Multiple sclerosis-associated retroviral agent (MSRV)-stimulated cytokine production in patients with relapsing-remitting multiple sclerosis

2009 ◽  
Vol 15 (4) ◽  
pp. 443-447 ◽  
Author(s):  
M Saresella ◽  
A Rolland ◽  
I Marventano ◽  
R Cavarretta ◽  
D Caputo ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Mononuclear Cells ◽  
Interleukin 10 ◽  
Interferon Γ ◽  
Endogenous Retroviruses ◽  
Peripheral Blood Mononuclear ◽  
Human Endogenous Retroviruses ◽  
Relapsing Remitting ◽  
Factor Α ◽  
Relapsing Remitting Multiple Sclerosis

Background Human endogenous retroviruses are suggested to play a pathogenic role in multiple sclerosis (MS); one of such retroviruses, the MS-associated retroviral agent (MSRV) has repeatedly been isolated in MS patients. Objective and methods We analyzed cytokine profiles in MSRV envelope protein (MSRV ENV-SU)-stimulated peripheral blood mononuclear cells of 30 relapsing-remitting MS patients with either acute (AMS) ( n = 13) or stable (SMS) ( n = 17) disease. Results suggest that MSRV ENV-SU induces the production of inflammatory cytokines, including tumor necrosis factor-α ( P < 0.05) and interferon-γ ( P < 0.004) in AMS patients and of interleukin-10 ( P < 0.05), an inflammation-dampening cytokine, in SMS individuals. Conclusions These data strengthen the hypothesis indicating that MSRV could be involved in the pathogenesis of MS.

Platelet depletion by anti-CD41 (αIIb) mAb injection early but not late in the course of disease protects against Plasmodium berghei pathogenesis by altering the levels of pathogenic cytokines

Blood ◽  
2005 ◽  
Vol 105 (5) ◽  
pp. 1956-1963 ◽  
Author(s):  
Henri C. van der Heyde ◽  
Irene Gramaglia ◽  
Guang Sun ◽  
Catherine Woods
Keyword(s):  
Plasmodium Berghei ◽  
Critical Role ◽  
Coagulation Factors ◽  
Interleukin 10 ◽  
Interferon Γ ◽  
Platelet Adherence ◽  
Large Numbers ◽  
Factor Α ◽  
Platelet Depletion ◽  
Platelet Microparticles

AbstractAccumulating evidence indicates that platelets play a critical role in the pathogenesis of experimental severe malaria (ESM) elicited by infection with Plasmodium berghei. Mice injected on day 1 of P berghei infection (early) with either anti-CD41 or anti-CD61 monoclonal antibodies (mAbs) exhibited significantly (P &lt; .001) increased survival from ESM compared with infection controls, indicating that platelets function early in the disease. In contrast, groups of mice treated on days 4, 5, and 6 (late) with anti-CD41 mAb exhibited similar mortality as controls. Because platelet depletion by anti-CD41 mAb on day 4 of infection did not protect mice, and platelet adherence occurs on day 6, platelet adherence to endothelium is not required to mediate malarial pathogenesis. Few platelet microparticles were detected in the blood during the course of malaria, but large numbers of erythrocyte vesicles, microparticles, and debris were detected. The protective effect of early anti-CD41 mAb treatment was independent of the number of platelets, platelet microparticles, erythrocyte-platelet conjugates, and erythrocyte vesicles. Mice treated early with anti-CD41 mAb exhibited markedly altered cytokine production on day 4 of P berghei infection (increased interleukin 10 [IL-10], IL-1α, IL-6, interferon-γ [IFN-γ], and tumor necrosis factor α [TNF-α]; decreased IL-2) but no decline in coagulation factors compared with rat immunoglobulin G (IgG)–treated controls, indicating that platelets regulate the levels of pathogenic cytokines.

The ability of Warburgia salutaris extracts to protect against crystalline silica-induced cell injury

2008 ◽  
Vol 27 (11) ◽  
pp. 827-835 ◽  
Author(s):  
M Leshwedi ◽  
V Steenkamp ◽  
M Dutton ◽  
M Gulumian
Keyword(s):  
Lipid Peroxidation ◽  
Transcription Factor ◽  
Cell Injury ◽  
Antioxidant Properties ◽  
Interferon Γ ◽  
Crystalline Silica ◽  
Protective Effects ◽  
Carcinogenic Effects ◽  
Dna Strand ◽  
Factor Α

In Southern Africa, the medicinal plant Warburgia salutaris is commonly used for the treatment of inflammatory and other diseases. The methanol extracts of W. salutaris were investigated with regard to a) production of proinflammatory cytokines tumor necrosis factor-α, interleukin-1β, and interferon-γ; b) activation of the transcription factor nuclear factor kappa B; and c) induction of deoxyribonucleic acid (DNA) damage and lipid peroxidation in the presence of crystalline silica particles. Due to its antioxidant properties, extracts of W. salutaris showed protective effects against crystalline silica-induced inflammatory cytokine expression, activation of nuclear transcription factor-κB, DNA strand breakage, and lipid peroxidation. Hence, W. salutaris may be a potential therapeutic agent against the fibrogenic and carcinogenic effects of crystalline silica.

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