scholarly journals NF-κB/ABCA1 Pathway Aggravates ox-LDL-Induced Cell Pyroptosis by Activation of NLRP3 Inflammasomes in THP-1-Derived Macrophages

Author(s):  
Jiashan Li ◽  
Jiaru Liu ◽  
Ying Yu ◽  
Yuee Liu ◽  
Xiuru Guan

Abstract There is now overwhelming experimental and clinical evidence that atherosclerosis is a chronic inflammatory disease and characterized by lipid deposition in blood vessels. Pyroptosis, an inflammatory form of cell death by certain inflammasomes, has been shown to be associated with the development of AS in recent years. However, the relationship between lipid deposition in foam cells and cell pyroptosis has not been clarified. Here, we demonstrate that with increasing ox-LDL concentration, the expression of pyroptosis associated protein GSDMD, NLRP3 inflammasome gradually increased, intracellular LDH and mature IL-1β release increased, and the proportion of double positive cells with Hoechst/PI staining increased. Interestingly, the expression of NF-κB signal activation marker protein p-NF-κB and p-IκB increased with the increase of ox-LDL concentration. Ox-LDL-induced pyroptosis can be abolished by NF-κB phosphorylation inhibitor, BAY11-7082. Additionally, BAY11-7082 could also significantly up-regulate the protein expression of ABCA1 and eliminate the inhibitory effect of ox-LDL on the expression of ABCA1.Moreover, siABCA1 was transfected into THP-1-derived macrophages under ox-LDL treatment. Compared with the control group, the expression of GSDMD and NLRP3 inflammasome, the release of mature IL-1β and LDH increased, and the proportion of Hoechst/PI staining double-positive cells increased with blocked cholesterol efflux. Finally, cells treated with VX-765, a pyroptosis inhibitor, showed increased cholesterol efflux and cell foaming in THP-1-derived macrophages,which suggest that cell pyroptosis may be a "double-edged sword" in the development of AS. In conclusion,our findings demonstrate for the first time that the NF-κB/ABCA1 pathway is involved in ox-LDL induced pyroptosis by cholesterol efflux blocked activation of NLRP3 inflammasomes in THP-1-derived macrophages, providing a new therapeutic avenue for the prevention and treatment of AS.

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Dong Zhang ◽  
Yin-long Li ◽  
Shu-you Wang ◽  
Xiao-dong Bai ◽  
Xiao-jing Song ◽  
...  

This study was to observe the effects of acupuncture and moxibustion on spectrum features of acupoint using hyperspectral imaging (HSI) technique. HSI of the Neiguan (PC6) in the acupuncture groups, moxibustion groups, and control groups was scanned by the hyperspectral imager to analyze the spectrum features and the variations within the wavelength of 400–1000 nm and explore the relationship between the spectral characteristics and effects of acupuncture and moxibustion. The light absorption intensity was slightly reduced within the wave band of 540–590 nm after acupuncture. The absorption intensity of PC6 before moxibustion was significantly higher than that after moxibustion, and the maximum reduction was found at the wavelength of 580 nm with 20.5% reduction,P<0.05. There was no significant change of the spectrum of palm and PC6 and the spectrum curves of the acupoint were basically identical in control group. The light absorption intensity of PC6 of human body was weakened after Acu-mox. Specific wavelengths were all exhibited at 580 nm and the effect of moxibustion was more significant. HSI technique can be used to measure the spectral characteristics of the acupoint areas. This first time research would be significant and beneficial for study on the effect of acupuncture and moxibustion.


Author(s):  
Yue Lang ◽  
Fengna Chu ◽  
Lingling Liu ◽  
Chao Zheng ◽  
Chunrong Li ◽  
...  

Abstract Multiple sclerosis (MS) is an inflammatory autoimmune demyelinating disease of the central nervous system. NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome, is implicated in the pathogenesis of MS and its animal model, experimental autoimmune encephalomyelitis (EAE). However, the exact mechanism by which NLRP3 inflammasome is involved in the development of MS and EAE is not clear. NF-kappaB (NF-κB) is associated with the activity of NLRP3 inflammasomes, but the role of NF-κB is controversial. We sought to demonstrate that both NF-κB and NLRP3 contribute to development of MS and EAE, and NF-κB pathway is positively correlated with NLRP3 activation in EAE. The inhibitor of NF-κB and NLRP3, BAY11-7082, can prevent and treat EAE. BAY11-7082 (5mg/kg/i.p and 20 mg/kg/i.p) was intraperitoneally administered to EAE mice at the time of second injection of pertussis toxin (BAY11-7082 prevention group) or at the onset of symptoms (BAY11-7082 treatment group). mRNA expressions of NLRP3 were determined by qPCR. Protein expressions of NLRP3, NF-κBp65, and phosphorylated-p65 were determined by Western blotting. Serum levels of inflammatory cytokines were measured by Cytometric Bead Array. Mice treated with BAY11-7082 (both prevention and treatment groups) showed lower clinical scores and attenuated pathological changes. NLRP3 inflammasome and activity of NF-κB in spinal cord of EAE mice was higher than that in control group. However, the level of NLRP3 inflammasome decreased in BAY11-7082 prevention and treatment groups. BAY11-7082 is a promising therapeutic agent for MS. NLRP3 activation in EAE maybe related with NF-κB pathway.


Author(s):  
Zhen Tao ◽  
Hongwei Guo ◽  
Jigang Tang ◽  
Ming Cheng

IntroductionSNW domain containing 1 (SNW1), as a splicing factor to regulate the activity of transcription factors, has been reported to be involved in multiple disease processes, including neuroblastoma. Whereas, the latent function and concrete mechanism of SNW1 in brain microvascular endothelial cells (BMECs) have not been clarified.Material and methodsBMECs were induced by oxidized low-density lipoprotein (ox-LDL), and high fat (HF)-fed rats were established. After SNW1 knockdown or NLR family pyrin domain containing 3 (NLRP3) overexpression, SNW1 and NLRP3 expressions were monitored via RT-qPCR, Western blot, or immunohistochemistry assays. Also, cell viability, apoptosis, and cholesterol efflux were determined via CCK-8, flow cytometry, and related kits; IL-18 and IL-3 levels were also certified by ELISA kits; and NLRP3 inflammasomes and cholesterol efflux-related proteins were identified by Western blot in vitro and in vivo.ResultsWe discovered that ox-LDL or HF-feeding significantly elevated SNW1 and NLRP3 expressions, and prominently induced BMECs injury in BMECs or rat brain tissues. Subsequently, our data confirmed that SNW1 knockdown markedly accelerated cholesterol efflux and viability, and prevented apoptosis and NLRP3 inflammasomes, which also could be reversed by NLRP3 overexpression in ox-LDL-induced BMECs. In addition, we showed that SNW1 knockdown could signally induce cholesterol efflux and repress NLRP3 inflammasome activation in HF-fed rats.ConclusionsWe demonstrated that SNW1 knockdown has a great protection effect on the dysfunction of BMECs by inhibiting NLRP3. So, SNW1 might be a therapeutic target for BMECs injury.


2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Yu Chen ◽  
Xingxiang He ◽  
Xinxu Yuan ◽  
Jinni Hong ◽  
Owais Bhat ◽  
...  

The Nod-like receptor protein 3 (NLRP3) inflammasome activation not only serves as an intracellular machinery triggering inflammation but also produces uncanonical effects beyond inflammation such as changing cell metabolism and increasing cell membrane permeability. The present study was designed to test whether this NLRP3 inflammasome activation contributes to the “two-hit” injury during nonalcoholic steatohepatitis (NASH) and whether it can be a therapeutic target for the action of Fufang Zhenzhu Tiaozhi (FTZ), a widely used herbal remedy for hyperlipidemia and metabolic syndrome in China. We first demonstrated that NLRP3 inflammasome formation and activation as well as lipid deposition occurred in the liver of mice on the high-fat diet (HFD), as shown by increased NLRP3 aggregation, enhanced production of IL-1β and high mobility group box 1 (HMGB1), and remarkable lipid deposition in liver cells. FTZ extracts not only significantly reduced the NLRP3 inflammasome formation and activation but also attenuated the liver steatosis and fibrogenic phenotype changed. In in vitro studies, palmitic acid (PA) was found to increase colocalization of NLRP3 components and enhanced caspase-1 activity in hepatic stellate cells (HSCs), indicating enhanced formation and activation of NLRP3 inflammasomes by PA. PA also increased lipid deposition. Nlrp3 siRNA can reverse this effect by silencing the NLRP3 inflammasome and both with FTZ. In FTZ-treated cells, not only inflammasome formation and activation was substantially attenuated but also lipid deposition in HSCs was blocked. This inhibition of FTZ on lipid deposition was similar to the effects of glycyrrhizin, an HMGB1 inhibitor. Mechanistically, stimulated membrane raft redox signaling platform formation and increased O2•− production by PA to activate NLRP3 inflammasomes in HSCs was blocked by FTZ treatment. It is concluded that FTZ extracts inhibit NASH by its action on both inflammatory response and liver lipid metabolism associated with NLRP3 inflammasome formation and activation.


2003 ◽  
Vol 62 (4) ◽  
pp. 241-249 ◽  
Author(s):  
M. Bolognini ◽  
B. Plancherel ◽  
J. Laget ◽  
P. Stéphan ◽  
O. Halfon

The aim of this study, which was carried out in the French-speacking part of Switzerland, was to examine the relationship between suicide attempts and self-mutilation by adolescents and young adults. The population, aged 14-25 years (N = 308), included a clinical sample of dependent subjects (drug abuse and eating disorders) compared to a control sample. On the basis of the Mini Neuropsychiatric Interview ( Sheehan et al., 1998 ), DSM-IV criteria were used for the inclusion of the clinical population. The results concerning the occurrence of suicide attempts as well as on self-mutilation confirm most of the hypotheses postulated: suicidal attempts and self-mutilation were more common in the clinical group compared to the control group, and there was a correlation between suicide attempts and self-mutilation. However, there was only a partial overlap, attesting that suicide and self-harm might correspond to two different types of behaviour.


2016 ◽  
Vol 37 (4) ◽  
pp. 213-222 ◽  
Author(s):  
Hansjörg Znoj ◽  
Sandra Abegglen ◽  
Ulrike Buchkremer ◽  
Michael Linden

Abstract. There is a growing interest in embitterment as psychological concept. However, little systematic research has been conducted to characterize this emotional reaction. Still, there is an ongoing debate about the distinctiveness of embitterment and its dimensions. Additionally, a categorical and a dimensional perspective on embitterment have been developed independently over the last decade. The present study investigates the dimensions of embitterment by bringing these two different approaches together, for the first time. The Bern Embitterment Inventory (BEI) was given to 49 patients diagnosed with “Posttraumatic Embitterment Disorder (PTED)” and a matched control group of 49 patients with psychological disorders with other dominant emotional dysregulations. The ability to discriminate between the two groups was assessed by t-tests and Receiver Operating Characteristic Curves (ROC curve analysis). PTED patients scored significantly higher on the BEI than the patients of the control group. ROC analyses indicated diagnostic accuracy of the inventory. Further, we conducted Confirmatory Factor Analyses (CFA) to examine the different dimensions of embitterment and their relations. As a result, we found four characteristic dimensions of embitterment, namely disappointment, lack of acknowledge, pessimism, and misanthropy. In general, our findings showed a common understanding of embitterment as a unique but multidimensional emotional reaction to distressful life-events.


2011 ◽  
Vol 10 (3) ◽  
pp. 139-143 ◽  
Author(s):  
Gazi Islam ◽  
Sarah E. S. Zilenovsky

This note examines the relationship between affirmative action (AA) program perceptions and women’s self-ascribed capacity and desire to become leaders. We propose that women who believe that their organization implements a program of preferential selection toward women will experience negative psychological effects leading to lowered self-expectations for leadership, but that this effect will be moderated by their justice perceptions of AA programs. We test this proposition empirically for the first time with a Latin American female sample. Among Brazilian women managers, desire but not self-ascribed capacity to lead was reduced when they believed an AA policy was in place. Both desire’s and capacity’s relationships with belief in an AA policy were moderated by justice perceptions.


1981 ◽  
Vol 96 (2) ◽  
pp. 273-280 ◽  
Author(s):  
Mridula Chowdhury ◽  
Robert Tcholakian ◽  
Emil Steinberger

Abstract. It has been suggested that treatment of intact male rats with oestradiol benzoate (OeB) causes an interference with testosterone (T) production by the testes by a direct inhibitory effect on steroidogenesis. To test this hypothesis, different doses (5, 10 or 25 IU) of hCG were administered concomitantly with 50 μg of OeB to adult intact or hypophysectomized male rats. The testicular and plasma testosterone, and serum hCG levels were determined. The sex accessory weights were recorded. In the intact OeB-treated group of animals, hCG stimulated both the secondary sex organs and plasma testosterone levels above the intact control group. However, in hypophysectomized animals, although plasma testosterone levels increased above that of intact controls, their secondary sex organ weights did not. Moreover, inspite of high circulating hCG levels, the testicular testosterone content and concentration remained suppressed in OeB-treated animals. The reason for such dichotomy of hCG action on OeB-treated animals is not clear at present.


2020 ◽  
Vol 7 (2) ◽  
pp. 247-255
Author(s):  
Maria Magdalena Setyaningsih ◽  
Emy Sutiyarsih

Kehamilan remaja adalah kehamilan yang terjadi pada remaja berusia kurang dari 20 tahunan. Kehamilan remaja memberikan banyak kerugian bagi kesehatan, mental dan psikologis, kesejahteraan ekonomi dan peluang karier, kemiskinan dan prospek kehidupan masa depan remaja. Tujuan penelitian mengidentifikasi faktor determinan yang melatarbelakangi terjadinya kehamilan remaja. Jenis penelitian adalah penelitian analitik kategorik jenis survei kuantitatif dengan desain case control. Populasi semua perempuan yang bertempat tinggal di wilayah dusun Wonosari, Sukosari, dan Krajan Pandansari dan pernah/sedang hamil pertama kali pada usia kurang dari 20 tahun. Teknik pengambilan sampel cluster random sampling besar sampel 73. Berdasarkan hasil model akhir analisis multivariat, diketahui bahwa variabel pendidikan, riwayat kehamilan remaja pada keluarga dan usia menikah merupakan variabel yang berhubungan dengan kejadian kehamilan remaja setelah dikontrol oleh variabel akses informasi, responden berpendidikan rendah memiliki peluang 20,8 kali lebih tinggi, responden yang memiliki riwayat kehamilan remaja pada keluarga memiliki peluang 14,9 kali lebih tinggi, responden yang menikah pada usia <20 tahun memiliki peluang 12,1 kali lebih tinggi, responden dengan pemahaman yang kurang baik terkait penggunaan kondom memiliki peluang 5,9 kali lebih tinggi untuk terjadi kehamilan remaja. Oleh karena itu perlu dibangun karakter buiding, sosial karakter suport untuk para ibu remaja dan keluarga sehingga terbangun interaksi yang baik dalam keluarga yang dilandasi dengan pendidikan dan pemahaman yang baik tentang Pendidikan seksualitas. Teen pregnancy is a pregnancy that occurs in adolescents aged less than 20 years old. Teen pregnancy provides many disadvantages for health, mental, psychological, economic well-being, career opportunities, poverty, and the future life. The aim of the study was to identify the determinants underlying teen pregnancy incidence. This study was a quantitative study with categorical analytic method. The study design used a case control with two comparison groups. The groups were control group and case group. The population in this study was all women who lived in the Wonosari, Sukosari, and Krajan Pandansari district and had or were pregnant for the first time at the age of less than 20 years old. Seventy three respondents were recruited using cluster sampling technique. The case group consists of women who were or had pregnant for the first time at the age of less than 20 years old and their children are currently aged ≤ 1 years old. The control group consists of women who were pregnant for the first time at the age of > 20 years old. The data was collected using a questionnaire. The findings showed that education, history of teen pregnancy in family and the age of marriage were related to the incidence of teen pregnancy after being controlled by information access. Low-educated respondents had 20.8 times higher chance of experiencing teen pregnancy; respondents with a history of teen pregnancy in the family had 4.9 times higher chance of experiencing teen pregnancy; respondents who were married at the age of < 20 years old had 12.1 times higher chance of experiencing teen pregnancy; respondents with poor understanding of condom use had 5.9 times higher chance of teenage pregnancy. In conclusion, the findings suggest to build good interactions in the family based on education and a good understanding of sex education.


2016 ◽  
Vol 1 (4) ◽  
Author(s):  
Hartini Tiono

Ulcerative colitis is a chronic inflammatory disease mainly affects sigmoid colon and rectum. The inflammation process will activate NF-κB and leads to proinflamatory cytokine release such as Interleukin-6 (IL-6). Fig leaves contain a high level of flavonoid which can prevent NF-κB activation, and further inhibits IL-6 secretion. This research aims to see the preventive effect of methanolic extract of fig leaves towards colon histopathological feature and IL-6 serum level on ulcerative colitis induced mice. Balb/C male mice were randomly assigned into 5 groups (n=5). The treatment groups were dextran suphate sodium (DSS) control group (group I), methanolic extract of Fig leaves dose 28 mg/ day control group (group II), and methanolic extract of Fig leaves dose 7 mg/ day (group III), 14 mg/ day (group IV), and 28 mg/ day (group V) for 14 days, which at the 8th till 14th day were given DSS to induce colitis. The results showed that both of colon mucosal damage and IL-6 serum level of group I were significantly different from other groups (p=0,029). In  conclusion, the methanolic extract of Fig leaves can improve colon mucous damage and decrease IL-6 serum level on ulcerative colitis-induced mice. Keywords: ulcerative colitis, fig leaves, colon mucousal damage, interleukin-6


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