Tumor Necrosis Factor, α-Induced Protein 3 Interacting Protein 2 is Involved in the Inflammatory Response in Sepsis via Inhibiting the Nuclear Factor-κB Pathway Activation

2020 ◽  
Vol 10 (4) ◽  
pp. 582-588
Author(s):  
Jia Li ◽  
Ye He ◽  
Yuping Li

The study aimed to explore the role of TNFAIP3 interacting protein 2 (TNIP2) in lipopolysaccharide (LPS) induced RAW264.7 macrophages or septic mice. TNIP2 level was detected using quantitative real time polymerase chain reaction (qRT-PCR) and western blotting. LPS-stimulated RAW264.7 macrophages were used to investigate the effects of TNIP2 on sepsis in vitro. In addition, septic mice model was established to validate the regulation of TNIP2 during inflammation response in vivo. The levels of inflammatory cytokines were assessed by enzyme-linked immunosorbent assay (ELISA). The data indicated that TNIP2 mRNA was down-regulated in the peripheral blood from sepsis patients. Interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α levels were significantly increased and the level of TNIP2 was suppressed in LPS-stimulated macrophages compared to the control group. TNIP2-plasmid promoted the TNIP2 expression in RAW 264.7 macrophages and reversed the effects of LPS on inflammatory factors and Nuclear factor-κ B (NFκ- B) pathway. The results also showed that TNIP2-plasmid alleviated inflammatory responses in septic mice, evidenced by the reduction in the levels of TNF-α , IL-1β and IL-6. TNIP2-plasmid also reduced the secretion of organ damage markers in septic mice serum. Our data indicated that TNIP2 was involved in the inflammatory response in sepsis via inhibiting the NF-κ B pathway activation.

2021 ◽  
Vol 22 (5) ◽  
pp. 2609
Author(s):  
Guifeng Wang ◽  
Keiichi Hiramoto ◽  
Ning Ma ◽  
Nobuji Yoshikawa ◽  
Shiho Ohnishi ◽  
...  

Glycyrrhizin (GL), an important active ingredient of licorice root, which weakens the proinflammatory effects of high-mobility group box 1 (HMGB1) by blocking HMGB1 signaling. In this study, we investigated whether GL could suppress inflammation and carcinogenesis in an azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced murine model of colorectal cancer. ICR mice were divided into four groups (n = 5, each)—control group, GL group, colon cancer (CC) group, and GL-treated CC (CC + GL) group, and sacrificed after 20 weeks. Plasma levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α were measured using an enzyme-linked immunosorbent assay. The colonic tissue samples were immunohistochemically stained with DNA damage markers (8-nitroguanine and 8-oxo-7,8-dihydro-2′-deoxy-guanosine), inflammatory markers (COX-2 and HMGB1), and stem cell markers (YAP1 and SOX9). The average number of colonic tumors and the levels of IL-6 and TNF-α in the CC + GL group were significantly lower than those in the CC group. The levels of all inflammatory and cancer markers were significantly reduced in the CC + GL group. These results suggest that GL inhibits the inflammatory response by binding HMGB1, thereby inhibiting DNA damage and cancer stem cell proliferation and dedifferentiation. In conclusion, GL significantly attenuates the pathogenesis of AOM/DSS-induced colorectal cancer by inhibiting HMGB1-TLR4-NF-κB signaling.


Dose-Response ◽  
2020 ◽  
Vol 18 (3) ◽  
pp. 155932582093976 ◽  
Author(s):  
Li Wang ◽  
Shaowei Wang ◽  
Zhen Xing ◽  
Fulong Li ◽  
Jinliang Teng ◽  
...  

Objective: The purpose of this study was to explore the application of dexmedetomidine (Dex) in cardiopulmonary bypass. Methods: A total of 60 patients undergoing elective cardiopulmonary bypass were divided into control (C) group and Dex group. In the Dex group, appropriate amount of Dex was added into the membrane lung prefilling solution before anesthesia induction, while those in control group were given normal saline. The levels of mean arterial pressure (MAP) and heart rate (HR) at different times were measured. The levels of cardiac troponin I (CTNI), malondialdehyde (MDA), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α) at different points (T0/T1/T2/T3/T4) in both groups were measured by enzyme-linked immunosorbent assay kits. Results: The intraoperative and postoperative levels of MAP and HR in the 2 groups were significantly lower than those preoperatively ( P < .05). The levels of MAP and HR in the Dex group were significantly lower than those of the C group ( P < .05). The levels of CTNI/MDA/IL-6/TNF-α at different points in both groups were significantly higher than those at T0 ( P < .05). The serum levels of CTNI, MDA, IL-6, and TNF-α in the Dex group at T1/T2/T3/T4 were significantly lower than those in the C group ( P < .05). The rate of arrhythmia in the Dex group was significantly lower than that in the C group ( P < .05). Conclusion: Dexmedetomidine has a stable effect in cardiopulmonary priming solution.


2020 ◽  
Vol 14 (4) ◽  
pp. 1354-1366
Author(s):  
L.S.O. Linta ◽  
P. Gouthon ◽  
T. Hountohotegbe ◽  
F. Messan ◽  
B.K. Nouatin ◽  
...  

Les données liées aux réponses inflammatoires en situation de match chez les handballeurs qui pratiquent dans un environnement immunostimulant comme celui du Bénin, ne sont pas disponibles. Cette étude avait pour objectif de déterminer chez des handballeurs appartenant à l’élite du Bénin, les modifications des paramètres associés à la réponse inflammatoire, induites par une série de trois matchs expérimentaux. Il s’agit d’une étude d’intervention, entreprise avec 16 joueurs juniors (JJ) et seniors (JS), répartis de façon aléatoire en deux équipes A et B, qui se sont affrontées pendant ces matchs. La numération des leucocytes circulants a été déterminée, les interleukines Il-6, Il-10 et le tumor necrosis factor (TNF-α) ont été dosés avant, juste à la fin, puis 24 heures après le premier (Match 1) et le troisième (Match 3) matchs. Les accroissements des moyennes des leucocytes totaux, des neutrophiles, de l’IL-6, de l’IL-10 et du TNF-α enregistrés au cours du troisième match étaient plus importants (p ˂ 0,05) que ceux observés à la fin du premier. Après 24 heures de récupération, la restauration des lymphocytes était de 83,3%, celle des leucocytes totaux de 76,6%, celle des neutrophiles de 57,7%, celles du TNF-α, de l’IL-6, de l’IL-10, respectivement de 61,3%, 64,0% et 57,2%. La série de trois matchs a eu un effet cumulatif sur l’augmentation des moyennes des paramètres étudiés et la récupération 24 h après le dernier match n’a atteint 100% pour aucun d’eux. Il est donc impérieux que des travaux soient réalisés à brève échéance, pour déterminer la méthode d’entraînement qui induit à la fois le développement des capacités physiques et la récupération rapide du système immunitaire en période d’entraînement et de compétition chez ces joueurs.Mots clés : Leucocytes, cytokines, compétition, Afrique subsaharienne. English Title: Inflammatory responses during a series of matches among elite handball players in BeninData related to inflammatory responses in match situations among handball players who practice in an immunostimulating environment such as the one in the Republic of Benin are not available. The aim of this study was to determine among elite male handball players, the changes in the parameters associated with the inflammatory response, induced by a series of three experimental matches. This research was an intervention study, undertaken with 16 junior (JP) and senior (SP) players, randomly assigned to two teams A and B for the experimental matches. Circulating leukocyte counts were determined, interleukins Il-6, Il-10, and tumor necrosis factor (TNF-α) were measured before, just at the end, and 24 hours after the first (Match 1) and the third (Match 3) matches. The increases in the averages of total leukocyte, neutrophil counts, the IL-6, IL-10 and TNF-α concentrations recorded during the third match were greater (p ˂ 0.05) than those observed at the end of the first. After 24 hours from the end, lymphocyte recovery was 83.3%, total leukocyte counts recovery was 76.6%, that of neutrophils was 57.7%. The TNF-α, IL-6 and IL-10 concentrations were respectively restored at 61.3%, 64.0%, and 57.2%. The three-match series had a cumulative effect on the increase in the mean values of the parameters studied. The 24 hours recovery following the last match was insufficient for 100% restoration of the inflammatory response makers. Therefore, it is imperative to carry out studies to determine a training method that induces both development of physical capacities and rapid recovery of the immune system during training sessions’ and competitions’ in these players.Keywords: Leukocytes, cytokines, competition, sub-Saharan Africa.


Author(s):  
Rui Liu ◽  
Ashleigh King ◽  
David Tarlinton ◽  
Jörg Heierhorst

Toll-like receptors (TLRs) and IL-1 receptors regulate immune and inflammatory responses by activating the nuclear factor (NF)-κB pathway. Here we report that B cell-specific loss of Dynein light chain-1 (DYNLL1, LC8) or its designated transcription factor ASCIZ (ATMIN) leads to severely reduced in vivo antibody responses to TLR4-dependent but not T cell-dependent antigens in mice. This defect was independent of DYNLL1’s established roles in modulating BIM-dependent apoptosis and 53BP1-dependent antibody class-switch recombination. In B cells and fibroblasts, the ASCIZ-DYNLL1 axis was required for TLR4-, IL-1- and CD40-mediated NF-κB pathway activation but dispensable for antigen receptor and TNF-α signalling. In contrast to previous reports that overexpressed DYNLL1 directly inhibits the phosphorylation and degradation of the NF-κB inhibitor IκBα, we found here that - under physiological conditions - DYNLL1 is required for signal-specific activation of the NF-κB pathway upstream of IκBα. Our data identify DYNLL1 as a signal-specific regulator of the NF-κB pathway and indicate that it may act as a universal modulator of TLR4 (and IL-1) signalling with wide-ranging roles in inflammation and immunity.


2021 ◽  
Vol 37 (1) ◽  
Author(s):  
Yun Ju Choi ◽  
Ji Eun Kim ◽  
Su Jin Lee ◽  
Jeong Eun Gong ◽  
You Jeong Jin ◽  
...  

Abstract Background The oral administration of polystyrene-microplastics (PS-MPs) causes chronic constipation of ICR mice, but there are no reports on their effects on the inflammatory response in the colon. To determine if the oral administration of MPs causes inflammation in the colon, the changes in the apoptosis-associated speck like protein containing a caspase recruitment domain (ASC)-inflammasome pathway, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway, and inflammatory cytokine expression were evaluated in the mid colon of ICR mice treated with 0.5 μm size PS-MPs for two weeks. Results The thicknesses of the mucosa, muscle, flat luminal surface, and crypt layer were decreased significantly (p < 0.01) in the mid colon of the MPs treated group compared to the Vehicle treated group. On the other hand, a remarkable increase in the expression levels of NOD-like receptor pyrin domain-containing protein (NLRP) 3, ASC, and Cleaved Caspase (Cas)-1 protein was observed in the MPs treated group. In addition, similar increasing pattern in the levels of p-NF-κB and phospho-inhibitory subunit of NF-κB (p-IkB) α protein was detected. Four inflammatory cytokines, including NF-κB, interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1β, showed an increased expression level after the MPs treatment. Conclusions Therefore, the present study suggests that PS-MPs can be a novel cause of an inflammatory response in the mid colon of ICR mice.


2003 ◽  
Vol 370 (3) ◽  
pp. 1011-1017 ◽  
Author(s):  
YunJin JUNG ◽  
Jennifer S. ISAACS ◽  
Sunmin LEE ◽  
Jane TREPEL ◽  
Zheng-gang LIU ◽  
...  

Tumour necrosis factor α (TNF-α) binds to its receptor (TNFR1) and activates both death- and inflammation/survival-related signalling pathways. The inflammation and survival-related signalling cascade results in the activation of the transcription factor, nuclear factor κB (NF-κB) and requires recruitment of receptor-interacting protein (RIP) to TNFR1. The indispensable role of RIP in TNF-induced NF-κB activation has been demonstrated in RIP-/- mice and in cell lines derived from such mice. In the present study, we show that the TNF-α-induced accumulation of hypoxia-inducible factor 1α (HIF-1α) protein in normoxic cells is RIP-dependent. Exposing fibroblasts derived from RIP-/- mice to either cobalt or PMA resulted in an equivalent HIF-1α induction to that seen in RIP+/+ fibroblasts. In contrast, RIP-/- cells were unable to induce HIF-1α in response to TNF-α. Further, transient transfection of NIH 3T3 cells with an NF-κB super-repressor plasmid (an inhibitor of NF-κB activation) also prevented HIF-1α induction by TNF-α. Surprisingly, although HIF-1α mRNA levels remained unchanged after induction by TNF, induction of HIF-1α protein by the cytokine was completely blocked by pretreatment with the transcription inhibitors actinomycin D and 5,6-dichlorobenzimidazole riboside. Finally, TNF failed to induce both HIF-1α, made resistant to von Hippel—Lindau (VHL), and wild-type HIF-1α transfected into VHL-/- cells. These results indicate that HIF-1α induction by TNF-α in normoxic cells is mediated by protein stabilization but is nonetheless uniquely dependent on NF-κB-driven transcription. Thus the results describe a novel mechanism of HIF-1α up-regulation and they identify HIF-1α as a unique component of the NF-κB-mediated inflammatory/survival response.


2021 ◽  
Vol 16 (1) ◽  
pp. 128-141
Author(s):  
Gang Xiao ◽  
Mei Zhang ◽  
Xing Peng ◽  
Guangyuan Jiang

Abstract Our current research aims to examine whether protocatechuic acid (PCA) can be used as a therapeutic agent for the development of cerebral aneurysm (CA) and to elucidate the mechanisms behind this. We assessed the effects of PCA at 50 and 100 mg/kg on the activation of signaling pathways for tissue necrosis factor (TNF)-α/nuclear factor (NF)-κB/nuclear factor erythroid 2 (Nrf-2) on progression and development in an elastase-induced CA model, accompanied by a high-salt diet to induce hypertension. The expression of inflammatory cytokines, chemokines, tumor necrosis factor-α, interleukins (IL)-8, IL-17, IL-6, IL-1β, and matrix metalloproteinase (MMP)-2 and MMP-9 was analyzed by ELISA, western blot, and reverse transcriptase quantative polymerase chain reaction. The expression levels of antioxidant enzymes and translocation of Nrf-2 were also determined. The group treated with PCA demonstrated a significant (P < 0.05) decrease in the aneurysmal size in rats compared to the CA-induced group. We found that PCA treatment suppressed the invasion of macrophage and activation of TNF-α/NF-κB/Nrf-2 signaling pathways. There was a significant decrease (P < 0.05) in pro-inflammatory cytokine and chemokine levels in a dose-dependent manner. We found that PCA treatment exerts protective effects by suppressing the development and progression of CA through the inhibition of inflammatory responses in macrophages via TNF-α/NF-κB/Nrf-2 signaling pathways, thus demonstrating that PCA can act as a treatment for CA.


2018 ◽  
Vol 16 ◽  
pp. 205873921881895
Author(s):  
Xiaolong Wu

The aim of this study was to investigate the expression of hypoxia-inducible factor-1α (HIF-1α) in keloids and its correlation with inflammatory responses and apoptosis. The keloid specimens resected in our hospital from November 2015 to February 2017 were selected as the pathological group, and the normal skin tissues from our hospital during the same period were selected as the control group. The expression of HIF-1α, inflammatory response cytokines, and apoptotic molecules in the tissues of two groups were detected. The messenger RNA (mRNA) expression of HIF-1α in the keloids in the pathological group was significantly higher than that in the control group, and the mRNA expression of interleukin (IL)-1β, IL-2, IL-6, and tumor necrosis factor (TNF)-α in the pathological group was significantly higher than those in the control group. The mRNA expression of Bax in the pathological group was significantly higher than that in the control group. The mRNA expression of Bcl-2, livin, and hPEBP4 in the pathological group was significantly lower than that in the control group. Pearson test showed that there was a positive correlation between the mRNA expression of HIF-1α and inflammatory cytokines including IL-1β, IL-2, IL-6, and TNF-α. There were also a positive correlation between the mRNA expression of HIF-1α and Bax and a negative correlation between the mRNA expression of HIF-1α and Bcl-2, livin, and hPEBP4. In conclusion, HIF-1α was highly expressed in keloids and closely related to inflammatory response cytokines and apoptosis molecules. Increased expression of HIF-1α in keloids may be an important factor in inflammatory responses and increased apoptosis in skin tissues.


Author(s):  
HAVRIZA VITRESIA ◽  
JAMSARI JAMSARI ◽  
GONDHOWIHARDJO T ◽  
ANDANI EKA PUTRA

Objective: The objective of the study was to determine the severity level of keratitis, inflammatory response, and clinical feature of fungal keratitis associated with tumor necrosis factor-alpha (TNF-α) and matrix metalloproteinase (MMP)-9 expression, with and without steroid administration. Methods: The mice corneas were inoculated with 108 CFU Candida albicans (CA), divided into two groups, one group with steroid administration and other group without steroid, and uninoculated cornea is used as the control. The mice eyes were observed for the development of keratitis and assess the clinical score to categorize severity level of the keratitis. After 7 days, they were enucleated for analysis of TNF-α and MMP-9 expression with immunohistochemistry and histopathologic examination. Results: Results show that the group inoculated with Candida and steroid has more moderate and severe level of keratitis compared to the group inoculated with Candida only. The final clinical score in the group of CA injected with steroid was 5–12 with mean 8.89 (2.67). The histopathological examination confirmed the presence of prominent inflammatory response in steroid group. The mean of TNF-α expression in Candida keratitis with and without steroid injections is 50.1 (8.09) and 31.7 (6.89) consecutively, compared to 16.8 (1.58) of control group. The mean of MMP-9 expression in Candida keratitis with steroid injection is higher than Candida keratitis group without steroid injection and control group, which are 46.6 (4.3), 37.8 (4.96), and 17.2 (1.73), respectively. This difference is statistically significant. Conclusion: Administration of steroids to Candida keratitis has negative effect to corneal tissue, resulting in more severe inflammatory response associated with increased TNF-α and MMP-9 expressions.


Perfusion ◽  
1998 ◽  
Vol 13 (5) ◽  
pp. 304-310 ◽  
Author(s):  
Wei Wang ◽  
Hui Ming Huang ◽  
De Ming Zhu ◽  
Hong Chen ◽  
Zhao Kang Su ◽  
...  

Cardiopulmonary bypass (CPB), a nonphysiological procedure, is associated with haemodilution and the inflammatory response, causing the accumulation of body water and organ dysfunction. The purpose of this study was to evaluate the efficacy of modified ultrafiltration. Forty paediatric patients undergoing cardiac operations were randomized into a control group and a modified ultrafiltration group. Blood cells, protein and cytokine concentrations were recorded for 24 h postoperatively. As the fluid was removed at 50 ml/min, both blood cells and protein were concentrated by modified ultrafiltration ( p < 0.001). The tumour necrosis factor (TNF)-α concentration was increased and interleukin-8 (IL-8) and endothelin (ET) concentrations were unaltered after ultrafiltration. After correction for albumin, TNF-α concentration changed little, and IL-8 and ET concentrations (36.75 ± 12.35, 42.89 ± 15.54) were decreased significantly (21.47 ± 13.87, 26.06 ± 12.54) after ultrafiltration. Modified ultrafiltration is an effective method for removing excess tissue fluid and concentrating blood after CPB. This technique can also filter out some cytokines.


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