scholarly journals IL-1β Inhibits TGFβ in the Temporomandibular Joint

2009 ◽  
Vol 88 (6) ◽  
pp. 557-562 ◽  
Author(s):  
W.H. Lim ◽  
J. Toothman ◽  
J.H. Miller ◽  
R.H. Tallents ◽  
S.M. Brouxhon ◽  
...  
Keyword(s):  
Mouse Model ◽  
Temporomandibular Joint ◽  
Inflammatory Cytokines ◽  
Tissue Regeneration ◽  
Inverse Correlation ◽  
Wild Type ◽  
Joint Pathology ◽  
Inflammatory Processes ◽  
Articular Pathology ◽  
Pro Inflammatory Cytokines

Similarly to humans, healthy, wild-type mice develop osteoarthritis, including of the temporomandibular joint (TMJ), as a result of aging. Pro-inflammatory cytokines, such as IL-1β, IL-6, and TNFα, are known to contribute to the development of osteoarthritis, whereas TGFβ has been associated with articular regeneration. We hypothesized that a balance between IL-1β and TGFβ underlies the development of TMJ osteoarthritis, whereby IL-1β signaling down-regulates TGFβ expression as part of disease pathology. Our studies in wild-type mice, as well as the Col1-IL1βXAT mouse model of osteoarthritis, demonstrated an inverse correlation between IL-1β and TGFβ expression in the TMJ. IL-1β etiologically correlated with joint pathology, whereas TGFβ expression associated with IL-1β down-regulation and improvement of articular pathology. Better understanding of the underlying inflammatory processes during disease will potentially enable us to harness inflammation for orofacial tissue regeneration.

Abstract 424: Phospholipid Transfer Protein Deficiency Promotes Inflammatory Factors' Expression via TLR4-TAK1-NFκB Pathway in Macrophage

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Yang Yu
Keyword(s):  
Inflammatory Cytokines ◽  
Inflammatory Factors ◽  
Phospholipid Transfer Protein ◽  
Wild Type ◽  
Transfer Protein ◽  
Phospholipid Transfer ◽  
Nfκb Pathway ◽  
Nuclear Levels ◽  
Deficient Mice ◽  
Pro Inflammatory Cytokines

Phospholipid transfer protein (PLTP) plays important roles in macrophage mediated inflammation. In the current study we observed that endogenous PLTP modulated pro-inflammatory pathways in macrophage. With the presence of LPS, peritoneal derived macrophage (PDM) or bone marrow derived macrophage (BMDM) from PLTP deficient mice (PLTP-/-) expressed significantly higher level of pro-inflammatory cytokines compared with PDM or BMDM from wild-type mice (WT), respectively. LPS induced TNFα expression in PLTP-/- BMDM or PLTP knockdown RAW264.7 were suppressed by (5Z)-7-Oxozeaenol, a TAK1 inhibitor, suggesting PLTP deficiency enhanced the expression of pro-inflammatory cytokines via TAK1-NFκB pathway in macrophage. Furthermore, abundance of TLR4 on the membrane was dramatically increased in BMDM from PLTP-/- compared with WT. In addition, inhibition of ABCA1 by chemical inhibitor, glyburide, did not reduce nuclear levels of active STAT3 of BMDM, which indicated that no autocrine PLTP triggered ABCA1-JAK2-STAT3 pathway in this study. In conclusion, PLTP deficiency or low expression may enhance LPS induced pro-inflammatory cytokines expression via TLR4-TAK1-NFκB pathway in macrophage.

scholarly journals WNT ligands contribute to the immune response during septic shock and amplify endotoxemia-driven inflammation in mice

2017 ◽  
Vol 1 (16) ◽  
pp. 1274-1286 ◽  
Author(s):  
Marcela Gatica-Andrades ◽  
Dimitrios Vagenas ◽  
Jessica Kling ◽  
Tam T. K. Nguyen ◽  
Helen Benham ◽  
...  
Keyword(s):  
Septic Shock ◽  
Immune Response ◽  
Mouse Model ◽  
Differential Expression ◽  
Inflammatory Cytokines ◽  
Key Points ◽  
Wnt Ligands ◽  
Pro Inflammatory Cytokines

Key Points Differential expression of WNT ligands in patients with septic shock and a mouse model of endotoxemia correlates with inflammatory cytokines. WNT ligands and WNT/β-catenin signaling positively regulate lipopolysaccharide-induced pro-inflammatory cytokines without impairing IL-10.

scholarly journals P069 CD73 promotes colitis-associated tumourigenesis in mice

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S170-S170
Author(s):  
X Wu ◽  
X Liu ◽  
N Lan ◽  
X Zheng ◽  
Y Chen ◽  
...  
Keyword(s):  
Weight Loss ◽  
Mouse Model ◽  
Rna Sequencing ◽  
Inflammatory Cytokines ◽  
Adenosine Receptors ◽  
Tumour Size ◽  
Body Weight Loss ◽  
Model Group ◽  
Adenosine Receptor Agonist ◽  
Pro Inflammatory Cytokines

Abstract Background Patients with inflammatory bowel disease (IBD) are at a higher risk of developing colitis-associated colorectal cancer. The aim of the present study was to investigate the role of CD73 in IBD-associated tumourigenesis. Methods A mouse model of colitis-associated tumourigenesis (CAT) induced by azoxymethane and dextran sulphate sodium (AOM/DSS) was successfully constructed. Model mice were injected with CD73 inhibitor or adenosine receptor agonist. Colon length, body weight loss and tumour formation were assessed macroscopically. Measurement of inflammatory cytokines and RNA sequencing on colon tissues were performed. Results Inhibition of CD73 by adenosine 5′-(α,β-methylene) diphosphate (APCP) suppressed the severity of CAT with attenuated weight loss, longer colons, lower tumour number and smaller tumour size when compared with the model group. On the other hand, activation of adenosine receptors using 1-(6-amino-9H-purin-9-yl)-1-deoxy-N-ethyl-β-d-ribofuranuronamide (NECA) exacerbated CAT. Histological assessment indicated that inhibition of CD73 reduced while activation of adenosine receptors exacerbated the histological damage of the colon compared with the model group. Increased expression of pro-inflammatory cytokines (tumour necrosis factor-α and interleukin-6) in colonic tissue was detected in the NECA group. According to the results of RNA sequencing, potential oncogenes such as ALOX15, Bcl2l15 and Nat8l were found to be downregulated in the APCP group and upregulated in the NECA group compared with the model group. Conclusion Therefore, inhibition of CD73 attenuated IBD-associated tumourigenesis, while activation of adenosine receptors exacerbated tumourigenesis in a C57BL/6J mouse model. This effect may be associated with the expression of pro-inflammatory cytokines and the regulation of ALOX15, Bcl2l15 and Nat8l.

scholarly journals Pro-Inflammatory Cytokines as Potential Early Biomarkers and Therapeutic Targets to Combat Ischemic Stroke

2020 ◽  
Vol 2 (11) ◽  
pp. 5-19
Author(s):  
Megha Agrawal ◽  
Keyword(s):  
Ischemic Stroke ◽  
Inflammatory Cytokines ◽  
Time Window ◽  
Medical Condition ◽  
Brain Area ◽  
Therapeutic Targets ◽  
Ongoing Research ◽  
Stroke Research ◽  
Inflammatory Processes ◽  
Pro Inflammatory Cytokines

Ischemic stroke is a serious medical condition and widely considered one of the most common causes of death and disability in the world today. There have been notable research advances in stroke so far and studies have shown that stroke’s complex pathophysiology process involves the oxidative stress and inflammatory reaction. However, despite the progress in stroke research, currently there are no established biochemical factors available that can be employed in the early diagnostics and intervention in stroke. Mostly, stroke diagnosis is based on neuroimaging, which is not a rapid tool to diagnose stroke. This decreases the survivability rate. Further, conventional therapeutic approaches for ischemic stroke management are based on restoring blood flow to the affected brain area and these therapies are effective only during a limited time window. Hence, this procedure results in benefiting only a very small percentage of patients. In view of these limitations, the ongoing research has focused on seeking alternative treatment methods that can reduce stroke brain damage and improve patients’ outcome. To this end, research goals are targeted towards gaining insights into the inflammatory response triggered by cerebral ischemia that is supposed to play an important role in the progression of stroke, and also the subsequent study of inflammatory molecules in the acute phase of stroke. In this mini-review, we describe the inflammatory processes occurring during ischemic stroke along with the potential for pro-inflammatory cytokines to become stroke biomarkers as well as interesting neuroprotective therapeutic targets that could be blocked or stimulated to modulate inflammation after stroke. Finally, we present a perspective briefly discussing some viewpoints on future studies in the ongoing field of stroke research.

scholarly journals Roles for B[a]P and FICZ in subchondral bone metabolism and experimental temporomandibular joint osteoarthritis via the AhR/Cyp1a1 signaling axis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yuri Yoshikawa ◽  
Takashi Izawa ◽  
Yusaku Hamada ◽  
Hiroko Takenaga ◽  
Ziyi Wang ◽  
...  
Keyword(s):  
Bone Loss ◽  
Mouse Model ◽  
Bone Metabolism ◽  
Temporomandibular Joint ◽  
Subchondral Bone ◽  
Dependent Manner ◽  
Bone Homeostasis ◽  
Wild Type ◽  
Temporomandibular Joint Osteoarthritis ◽  
Signaling Axis

AbstractBone loss due to smoking represents a major risk factor for fractures and bone osteoporosis. Signaling through the aryl hydrocarbon receptor (AhR) and its ligands contributes to both bone homeostasis and inflammatory diseases. It remains unclear whether the same AhR signaling axis affects the temporomandibular joint (TMJ). The aim of this study was to investigate possible mechanisms which mediate bone loss in the TMJ due to smoking. In particular, whether benzo[a]pyrene (B[a]P), a carcinogen of tobacco smoke, induces expression of the AhR target gene, Cyp1a1, in mandibular condyles. Possible functions of an endogenous ligand of FICZ, were also investigated in a TMJ-osteoarthritis (OA) mouse model. B[a]P was administered orally to wild-type and AhR−/− mice and bone metabolism was subsequently examined. TMJ-OA was induced in wild-type mice with forceful opening of the mouth. Therapeutic functions of FICZ were detected with μCT and histology. Exposure to B[a]P accelerated bone loss in the mandibular subchondral bone. This bone loss manifested with osteoclastic bone resorption and upregulated expression of Cyp1a1 in an AhR-dependent manner. In a mouse model of TMJ-OA, FICZ exhibited a dose-dependent rescue of mandibular subchondral bone loss by repressing osteoclast activity. Meanwhile, in vitro, pre-treatment with FICZ reduced RANKL-mediated osteoclastogenesis. B[a]P regulates mandibular subchondral bone metabolism via the Cyp1a1. The AhR ligand, FICZ, can prevent TMJ-OA by regulating osteoclast differentiation.

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