Abstract:
BACKGROUND:Inflammation, angiogenesis and oxidative stress have been implicated in the pathogenesis of various vascular diseases. Recent evidence suggests that dimethylfumarate (DMF), an antiposriatic and anti-multiple sclerosis agent, possesses anti-inflammatory, anti-oxidative and anti-angiogenic properties. Here, we analyze the influence of DMF on TNF-α-induced expression of the important pro-inflammatory and pro-atherogenic chemokine MCP-1 and investigate the underlying mechanisms of this expression. FINDINGS:We analyzed constitutive and TNF-α-induced expression of MCP-1 in human umbilical vascular endothelial cells (HUVEC) +/- DMF treatment via enzyme-linkes immunosorbent assay (ELISA). DMF significantly inhibited the protein expression levels in a time- and concentration-dependent manner. Furthermore, MCP-1 mRNA expression was also reduced in response to DMF, as demonstrated by RT-PCR. Thus, the regulation occurs at the transcriptional level. Interestingly, DMF prolonged the TNF-α-induced p38 and JNK phosphorylation in HUVEC, as demonstrated by Western blot analysis; however, the p38 and JNK inhibitor SB203580 did not affect the DMF-conveyed suppression of TNF-α-induced MCP-1 expression. DMF suppressed the TNF-α-induced nuclear translocation and phosphorylation (Serine 536) of p65 in these cells. These results were additionally approved by p65 luciferase promoter assays. Furthermore, we found that DMF slightly inhibited the early degradation of IκBα. In addition, we verified our results using other important inflammatory cytokines such as CCL-5, PDGF-BB, GM-CSF and IL-6. CONCLUSION:DMF suppresses various TNF-α-induced pro-inflammatory and pro-atherogenic cytokines/chemokines in human endothelial cells. This action is regulated by reduced p65 activity and nuclear translocation, which can be explained in part by the reduced early degradation of IκBα and more important the reduced phosphorylation of p65 at Serine 536. These effects were independent of the p38, PI3K and p42/44 signaling pathways. As a result, DMF might be suitable for treating patients with vascular diseases.
journal_name
J Inflamm (Lond)journal_title
Journal of inflammation (London, England)authors
Gerhardt S,König V,Doll M,Hailemariam-Jahn T,Hrgovic I,Zöller N,Kaufmann R,Kippenberger S,Meissner Mdoi
10.1186/s12950-015-0094-zsubject
Has Abstractpub_date
2015-08-06 00:00:00pages
49issn
1476-9255pii
94journal_volume
12pub_type
杂志文章abstract:BACKGROUND:Obesity configures a pathophysiological profile that predisposes the development of metabolic and cardiovascular diseases, critically impacting public health. The chronic dysregulation of immuno-metabolic components triggered by pediatric obesity is a common but scarcely understood aspect of the disease. Per...
journal_title:Journal of inflammation (London, England)
pub_type: 杂志文章
doi:10.1186/s12950-020-00264-2
更新日期:2020-10-31 00:00:00
abstract:BACKGROUND:The concept that a strong inflammatory response involving the full complement of cytokines and other mediators is critical for unimpaired healing has been challenged by wound healing studies using transgenic and knockout (KO) mice. The present study explored the effect of abrogation of the p40 subunit, which...
journal_title:Journal of inflammation (London, England)
pub_type: 杂志文章
doi:10.1186/1476-9255-8-39
更新日期:2011-12-20 00:00:00
abstract:BACKGROUND:Nuclear factor kappa B (NF-kappaB) has been shown to play an important role in regulating the expression of many genes involved in cell survival, immunity and in the inflammatory processes. NF-kappaB activation upregulates inducible nitric oxide synthase leading to enhanced nitric oxide production during an ...
journal_title:Journal of inflammation (London, England)
pub_type: 杂志文章
doi:10.1186/1476-9255-4-23
更新日期:2007-11-24 00:00:00
abstract:BACKGROUND:Airway inflammation and asthma have been linked to oxidative stress and the melastatin-related transient receptor potential cation channel, member 2 (TRPM2), which can be activated by reactive oxygen species (ROS), has emerged as a potential therapeutic target for inflammatory diseases. OBJECTIVE:Using TRPM...
journal_title:Journal of inflammation (London, England)
pub_type: 杂志文章
doi:10.1186/1476-9255-10-19
更新日期:2013-05-01 00:00:00
abstract:BACKGROUND:Hemorrhagic shock/resuscitation is associated with aberrant neutrophil activation and organ failure. This experimental porcine study was done to evaluate the effects of Fas-directed extracorporeal immune therapy with a leukocyte inhibition module (LIM) on hemodynamics, neutrophil tissue infiltration, and tis...
journal_title:Journal of inflammation (London, England)
pub_type: 杂志文章
doi:10.1186/1476-9255-7-18
更新日期:2010-04-20 00:00:00
abstract:BACKGROUND:124 triazolo [4, 3-a]18naphthyridine derivatives (including NF161 and NF177) were tested for anti-inflammatory, analgesic and antipyretic properties and for their effects on spontaneous locomotor activity in mice and acute gastrolesivity in rats. Both NF161 and NF177 appeared to be anti-inflammatory and anal...
journal_title:Journal of inflammation (London, England)
pub_type: 杂志文章
doi:10.1186/1476-9255-3-4
更新日期:2006-03-28 00:00:00
abstract::Qihong Que and colleagues found that liraglutide exhibited anti-inflammatory activity through the activation of the PKA/CREB pathway in an OA rat model. We believe there was a flaw in this research. In their first experiment, the sacrifice time of the 10 rats in the control group has not been stated. And when the rats...
journal_title:Journal of inflammation (London, England)
pub_type: 社论
doi:10.1186/s12950-019-0225-z
更新日期:2019-10-11 00:00:00
abstract:: We previously showed that the progression of burn-induced injury was inhibited by exposing the peripheral area of injured skin to sublethal hyperthermia following the burn. We called this phenomenon post-heat shock tolerance. Here we suggest a mechanism for this phenomenon. Exposure of the peripheral primary hyperalg...
journal_title:Journal of inflammation (London, England)
pub_type: 杂志文章
doi:10.1186/1476-9255-6-7
更新日期:2009-03-27 00:00:00
abstract:BACKGROUND:Cardiopulmonary bypass (CPB) is a commonly used technique in cardiac surgery. CPB is however associated with a strong induction of systemic inflammatory response syndrome (SIRS) which in conjunction with ischemia and reperfusion may lead to multiple organ failure. The aim of the study was to establish and ch...
journal_title:Journal of inflammation (London, England)
pub_type: 杂志文章
doi:10.1186/s12950-014-0026-3
更新日期:2014-08-12 00:00:00
abstract::Adult bone marrow derived mesenchymal stem cells offer the potential to open a new frontier in medicine. Regenerative medicine aims to replace effete cells in a broad range of conditions associated with damaged cartilage, bone, muscle, tendon and ligament. However the normal process of immune rejection of mismatched a...
journal_title:Journal of inflammation (London, England)
pub_type: 杂志文章
doi:10.1186/1476-9255-2-8
更新日期:2005-07-26 00:00:00
abstract:BACKGROUND:Chronic obstructive pulmonary disease is associated with numerous vascular effects including endothelial dysfunction, arterial stiffness and atherogenesis. It is also known that a decline in lung function is associated with increased cardiovascular comorbidity in smokers. The mechanism of this cardiopulmonar...
journal_title:Journal of inflammation (London, England)
pub_type: 杂志文章
doi:10.1186/1476-9255-7-34
更新日期:2010-07-22 00:00:00
abstract:BACKGROUND:The Amazonian medicinal plant Sangre de grado (Croton palanostigma) has traditional applications for the treatment of wound healing and inflammation. We sought to characterize two extracts (progrado and zangrado) in terms of safety and oligomeric proanthocyanidin chain length. Additionally progrado was evalu...
journal_title:Journal of inflammation (London, England)
pub_type: 杂志文章
doi:10.1186/1476-9255-4-16
更新日期:2007-08-14 00:00:00
abstract::Neonatal monocytes display immaturity of numerous functions compared with adult cells. Gene expression arrays provide a promising tool for elucidating mechanisms underlying neonatal immune function. We used a well-established microarray to analyze differences between LPS-stimulated human cord blood and adult monocytes...
journal_title:Journal of inflammation (London, England)
pub_type: 杂志文章
doi:10.1186/1476-9255-4-4
更新日期:2007-02-16 00:00:00
abstract:BACKGROUND:BMP4, a member of the transforming growth factor-beta superfamily, is upregulated in the aortas of diabetic db/db mice. However, little is known about its role in diabetic atherosclerosis. Therefore, we examined the roles of BMP4 in the formation of diabetic atherosclerosis in apolipoprotein E knockout (ApoE...
journal_title:Journal of inflammation (London, England)
pub_type: 杂志文章
doi:10.1186/1476-9255-10-32
更新日期:2013-10-09 00:00:00
abstract:BACKGROUND:Milk-derived bioactive peptides retain many biological properties and have therapeutic effects in cardiovascular disorders such as atherosclerosis. Under inflammatory conditions the expression of endothelial cells adhesion molecules is induced, increasing monocyte adhesion to human vessel wall, a critical st...
journal_title:Journal of inflammation (London, England)
pub_type: 杂志文章
doi:10.1186/s12950-014-0044-1
更新日期:2015-01-20 00:00:00
abstract:BACKGROUND:Captopril is an angiotensin-converting enzyme (ACE) inhibitor widely used in the treatment of arterial hypertension and cardiovascular diseases. Our objective was to study whether captopril is able to attenuate the cardiac inflammatory process associated with arterial hypertension. METHODS:Left ventricle mR...
journal_title:Journal of inflammation (London, England)
pub_type: 杂志文章
doi:10.1186/1476-9255-7-21
更新日期:2010-05-12 00:00:00
abstract:BACKGROUND:Circulating 25 hydroxyvitamin D (25 (OH)D), an accurate measure of vitamin D status, is markedly greater in individuals with increased exposure to ultraviolet B (UVB) light via sunlight or the use of artificial UV light. Aside from the known relationship between vitamin D and bone, vitamin D has also been im...
journal_title:Journal of inflammation (London, England)
pub_type: 杂志文章
doi:10.1186/1476-9255-5-10
更新日期:2008-07-24 00:00:00
abstract:BACKGROUND:PTPH1 is a protein tyrosine phosphatase expressed in T cells but its effect on immune response is still controversial. PTPH1 dephosphorylates TCRzeta in vitro, inhibiting the downstream inflammatory signaling pathway, however no immunological phenotype has been detected in primary T cells derived from PTPH1-...
journal_title:Journal of inflammation (London, England)
pub_type: 杂志文章
doi:10.1186/1476-9255-7-16
更新日期:2010-03-30 00:00:00
abstract:BACKGROUND:Wnt5A is released by activated macrophages and elevated levels have been detected in sepsis patients with severe systemic inflammation. However, the signalling and functional effects of Wnt5A in the vascular endothelial cells (VEC) remained unclear. Recently, we showed that Wnt5A affects barrier function in ...
journal_title:Journal of inflammation (London, England)
pub_type:
doi:10.1186/s12950-017-0157-4
更新日期:2017-05-19 00:00:00
abstract:BACKGROUND:CCR2 plays a key role in regulating monocyte trafficking to sites of inflammation and therefore has been the focus of much interest as a target for inflammatory disease. METHODS:Here we examined the effects of CCR2 blockade with a potent small molecule antagonist to determine the pharmacodynamic consequence...
journal_title:Journal of inflammation (London, England)
pub_type: 杂志文章
doi:10.1186/1476-9255-6-32
更新日期:2009-11-11 00:00:00
abstract::The critical role of inappropriate inflammation is becoming accepted in many diseases that affect man, including cardiovascular diseases, inflammatory and autoimmune disorders, neurodegenerative conditions, infection and cancer.This review proposes that cancer up-regulates the angiotensin II type 1 (AT1) receptor thro...
journal_title:Journal of inflammation (London, England)
pub_type: 杂志文章
doi:10.1186/1476-9255-1-3
更新日期:2004-09-30 00:00:00
abstract:BACKGROUND:Salivary histatins are bioactive peptides related to the innate immune system associated with antimicrobial activities. However, very little is known about the physiological and biological functions of histatins against host cells or their role in oral cell inflammation. Histatin 3 binds to heat shock cognat...
journal_title:Journal of inflammation (London, England)
pub_type: 杂志文章
doi:10.1186/1476-9255-11-4
更新日期:2014-02-04 00:00:00
abstract:BACKGROUND:Urinary bladder and renal dysfunction are secondary events associated with spinal cord injury (SCI) in humans. These secondary events not only compromise quality of life but also delay overall recovery from SCI pathophysiology. Furthermore, in experimental models the effects of SCI therapy on bladder and ren...
journal_title:Journal of inflammation (London, England)
pub_type: 杂志文章
doi:10.1186/1476-9255-7-17
更新日期:2010-04-19 00:00:00
abstract:BACKGROUND:Little is known about the time-course of the postprandial appearance of macronutrient-induced inflammatory response. Our aim was to investigate the postprandial inflammatory and metabolic response following high fat, high caloric popular meals in apparently healthy participants. METHODS:Fifty four apparentl...
journal_title:Journal of inflammation (London, England)
pub_type: 杂志文章
doi:10.1186/1476-9255-10-3
更新日期:2013-01-31 00:00:00
abstract::Cathelicidins are mammalian proteins containing a C-terminal cationic antimicrobial domain. Porcine PR-39 cathelicidin affects leukocyte biology. Mechanisms of action may involve alteration of heparan sulfate proteoglycan-dependent functions in inflammatory cells. It was tested whether PR-39 affects human neutrophil m...
journal_title:Journal of inflammation (London, England)
pub_type: 杂志文章
doi:10.1186/1476-9255-3-14
更新日期:2006-11-02 00:00:00
abstract:BACKGROUND:Homocysteine (Hcy) and inflammatory cytokines have been linked to adverse outcomes in persons with cardiovascular and kidney diseases and recent reports suggest that cytokine-mediated inflammatory infiltrates may be an important contributor to the pathogenesis the aforementioned diseases. Although some repor...
journal_title:Journal of inflammation (London, England)
pub_type: 杂志文章
doi:10.1186/1476-9255-6-27
更新日期:2009-09-26 00:00:00
abstract:Background:Impairment of the blood-brain barrier (BBB) in severe acute pancreatitis (SAP) could result in life-threatening pancreatic encephalopathy. Interleukin-10 (IL-10) is a classical cytokine that is well-known for its strong immunoregulatory and anti-inflammatory abilities. However, whether and how IL-10 protects...
journal_title:Journal of inflammation (London, England)
pub_type: 杂志文章
doi:10.1186/s12950-018-0180-0
更新日期:2018-02-27 00:00:00
abstract::IkappaBalpha is an inhibitor of the nuclear transcription factor NF-kappaB. Binding of IkappaBalpha to NF-kappaB inactivates the transcriptional activity of NF-kappaB. Expression of IkappaBalpha itself is regulated by NF-kappaB, which provides auto-regulation of this signaling pathway. Here we present a mouse model fo...
journal_title:Journal of inflammation (London, England)
pub_type: 杂志文章
doi:10.1186/1476-9255-2-10
更新日期:2005-10-05 00:00:00
abstract:: Tumor necrosis factor alpha (TNF-alpha)is a host inflammatory factor. Bacteria increase TNF-alpha expression in a variety of human diseases including infectious diseases, inflammatory bowel diseases, and cancer. It is unknown, however, how TNF-alpha directly modulates bacterial protein expression during intestinal in...
journal_title:Journal of inflammation (London, England)
pub_type: 杂志文章
doi:10.1186/1476-9255-7-42
更新日期:2010-08-12 00:00:00
abstract:Background:The relationship between chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and erectile dysfunction (ED) has been shown in many studies. However, the specific mechanism remains unclear. This study was to investigate the corpus cavernosum smooth muscle cell function and phenotype transformation in Ex...
journal_title:Journal of inflammation (London, England)
pub_type: 杂志文章
doi:10.1186/s12950-019-0233-z
更新日期:2020-01-06 00:00:00