scholarly journals Inflammatory Cytokines IL-1β and TNF-α Regulate p75NTR Expression in CNS Neurons and Astrocytes by Distinct Cell-Type-Specific Signalling Mechanisms

ASN NEURO ◽  
2009 ◽  
Vol 1 (2) ◽  
pp. AN20090009 ◽  
Author(s):  
Soyoung Choi ◽  
Wilma J Friedman

The p75NTR (where NTR is neurotrophin receptor) can mediate many distinct cellular functions, including cell survival and apoptosis, axonal growth and cell proliferation, depending on the cellular context. This multifunctional receptor is widely expressed in the CNS (central nervous system) during development, but its expression is restricted in the adult brain. However, p75NTR is induced by a variety of pathophysiological insults, including seizures, lesions and degenerative disease. We have demonstrated previously that p75NTR is induced by seizures in neurons, where it induces apoptosis, and in astrocytes, where it may regulate proliferation. In the present study, we have investigated whether the inflammatory cytokines IL (interleukin)-1 β and TNF- α (tumour necrosis factor- α), that are commonly elevated in these pathological conditions, mediate the regulation of p75NTR in neurons and astrocytes. We have further analysed the signal transduction pathways by which these cytokines induce p75NTR expression in the different cell types, specifically investigating the roles of the NF- κB (nuclear factor κB) and p38 MAPK (mitogen-activated protein kinase) pathways. We have demonstrated that both cytokines regulate p75NTR expression; however, the mechanisms governing this regulation are cytokine- and cell-type specific. The distinct mechanisms of cytokine-mediated p75NTR regulation that we demonstrate in the present study may facilitate therapeutic intervention in regulation of this receptor in a cell-selective manner.

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 856
Author(s):  
Eui-Jeong Han ◽  
Ilekuttige Priyan Shanura Fernando ◽  
Hyun-Soo Kim ◽  
Dae-Sung Lee ◽  
Areum Kim ◽  
...  

The present study evaluated the effects of (–)-loliolide isolated from Sargassum horneri (S. horneri) against oxidative stress and inflammation, and its biological mechanism in interferon (IFN)-γ/tumor necrosis factor (TNF)-α-stimulated HaCaT keratinocytes. The results showed that (–)-loliolide improved the cell viability by reducing the production of intracellular reactive oxygen species (ROS) in IFN-γ/TNF-α-stimulated HaCaT keratinocytes. In addition, (–)-loliolide effectively decreased the expression of inflammatory cytokines (interleukin (IL)-4 IL-6, IL-13, IFN-γ and TNF-α) and chemokines (CCL11 (Eotaxin), macrophage-derived chemokine (MDC), regulated on activation, normal T cell expressed and secreted (RANTES), and thymus and activation-regulated chemokine (TARC)), by downregulating the expression of epidermal-derived initial cytokines (IL-25, IL-33 and thymic stromal lymphopoietin (TSLP)). Furthermore, (–)-loliolide suppressed the activation of mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling, whereas it activated nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling. Interestingly, the cytoprotective effects of (–)-loliolide against IFN-γ/TNF-α stimulation were significantly blocked upon inhibition of HO-1. Taken together, these results suggest that (–)-loliolide effectively suppressed the oxidative stress and inflammation by activating the Nrf2/HO-1 signaling in IFN-γ/TNF-α-stimulated HaCaT keratinocytes.


2000 ◽  
Vol 191 (8) ◽  
pp. 1281-1292 ◽  
Author(s):  
Raelene J. Grumont ◽  
Steve Gerondakis

In lymphocytes, the Rel transcription factor is essential in establishing a pattern of gene expression that promotes cell proliferation, survival, and differentiation. Here we show that mitogen-induced expression of interferon (IFN) regulatory factor 4 (IRF-4), a lymphoid-specific member of the IFN family of transcription factors, is Rel dependent. Consistent with IRF-4 functioning as a repressor of IFN-induced gene expression, the absence of IRF-4 expression in c-rel−/− B cells coincided with a greater sensitivity of these cells to the antiproliferative activity of IFNs. In turn, enforced expression of an IRF-4 transgene restored IFN modulated c-rel−/− B cell proliferation to that of wild-type cells. This cross-regulation between two different signaling pathways represents a novel mechanism that Rel/nuclear factor κB can repress the transcription of IFN-regulated genes in a cell type–specific manner.


2001 ◽  
Vol 281 (6) ◽  
pp. G1405-G1412 ◽  
Author(s):  
T. Suzuki ◽  
E. Grand ◽  
C. Bowman ◽  
J. L. Merchant ◽  
A. Todisco ◽  
...  

Helicobacter pyloriand proinflammatory cytokines have a direct stimulatory effect on gastrin release from isolated G cells, but little is known about the mechanism by which these factors regulate gastrin gene expression. We explored whether tumor necrosis factor (TNF)-α and interleukin (IL)-1 directly regulate gastrin gene expression and, if so, by what mechanism. TNF-α and IL-1 significantly increased gastrin mRNA in canine G cells to 181 ± 18% and 187 ± 28% of control, respectively, after 24 h of treatment. TNF-α and IL-1 stimulated gastrin promoter activity to a maximal level of 285 ± 12% and 415 ± 26% of control. PD-98059 (a mitogen-activated protein kinase kinase inhibitor), SB-202190 (a p38 kinase inhibitor), and GF-109203 (a protein kinase C inhibitor) inhibited the stimulatory action of both cytokines on the gastrin promoter. In conclusion, both cytokines can directly regulate gastrin gene expression via a mitogen-activated protein kinase- and protein kinase C-dependent mechanism. These data suggest that TNF-α and IL-1 may play a direct role in Helicobacter pylori-induced hypergastrinemia.


2021 ◽  
Vol 19 (3) ◽  
pp. 467-476
Author(s):  
Jung-Soon Han

Purpose: This study investigated the nutritional value of Misutkaru with added Gryllus bimaculatus powder (GBM) and its applicability as a healthy functional food.Methods: Chemical analysis of the moisture, crude fat, protein, and mineral contents was performed in accordance with the Association of Official Analytical Chemists (AOAC) guidelines. The amino acid and fatty acid compositions were analyzed using an automatic amino acid analyzer and gas chromatography, respectively. The levels of inflammatory cytokines tumor necrosis factor‑alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL‑6) induced by lipopolysaccharides in RAW 264.7 cells were measured.Results: The general composition per 100 g of GBM was 41.87 g protein, 19.75 g fat, and 28.52 g carbohydrates. The mineral content per 100 g of GBM was 889.66 mg calcium, 1189.73 mg potassium, 220.36 mg magnesium, 207.51 mg sodium, 694.81 mg phosphorus, and 15.50 mg zinc. In particular, valine (21.361 mg/kg), leucine (29.180 mg/kg), and isoleucine (15.562 mg/kg) were abundant in GBM. GBM also effectively downregulated the production of the inflammatory cytokines TNF-α, IL-1β, and IL-6 in RAW 264.7 macrophages.Conclusion: Misutkaru with added Gryllus bimaculatus powder may have potential for application in the development of food materials or foods to prevent muscle loss in elderly individuals and sarcopenia patients, build muscle, and prevent increase in blood lipid concentrations in middle aged people. In particular, as Gryllus bimaculatus is low in fat and carbohydrates, it can be used as a diet material.


2001 ◽  
Vol 281 (2) ◽  
pp. H661-H668 ◽  
Author(s):  
Kristina Detmer ◽  
Zhongbiao Wang ◽  
Debra Warejcka ◽  
Sandra K. Leeper-Woodford ◽  
Walter H. Newman

Because inflammatory processes may promote the development of atherosclerosis, we examined the activation of cytokine genes in rat vascular smooth muscle cells in vitro after treatment with bacterial lipopolysaccharide (LPS). Interleukin-1 (IL-1), IL-6 and tumor necrosis factor-α (TNF-α) mRNA increased in response to LPS. Activation of nuclear factor-κB (NF-κB) presumably results in NF-κB binding to regulatory regions of target genes and activating transcription. We therefore compared the kinetics of NF-κB activation, cytokine message production, and TNF-α secretion. Maximum active NF-κB was found at 30 min after the addition of LPS and decreased thereafter. Increased IL-6 mRNA was detected at 30 min, increased TNF-α mRNA at 60 min, and increased IL-1 mRNA at 120 min. Secretion of TNF-α was dependent on LPS concentration and was first detected 120 min after LPS addition. Aspirin, which has been shown to inhibit NF-κB activation and cytokine secretion in other cell types, did not inhibit NF-κB activation or TNF-α secretion. However, aspirin reduced the amount of both TNF-α and IL-6 mRNA present 30 min after LPS addition by half ( P < 0.05).


Immunity ◽  
2019 ◽  
Vol 50 (2) ◽  
pp. 317-333.e6 ◽  
Author(s):  
Xiaoyu Liu ◽  
Daniel P. Nemeth ◽  
Daniel B. McKim ◽  
Ling Zhu ◽  
Damon J. DiSabato ◽  
...  

1999 ◽  
Vol 274 (40) ◽  
pp. 28697-28707 ◽  
Author(s):  
Robert M. Tjin Tham Sjin ◽  
Kenneth A. Lord ◽  
Abbas Abdollahi ◽  
Barbara Hoffman ◽  
Dan A. Liebermann

2003 ◽  
Vol 31 (6) ◽  
pp. 1462-1471 ◽  
Author(s):  
S.K. Dower ◽  
E.E. Qwarnstrom

We have been analysing the signalling systems that couple to receptors of the TIR (Toll/interleukin-1 receptor) family, which signal through a common cytoplasm region; the TIR domain. These systems are of both practical and fundamental biological significance, being central to the pathogenesis of chronic inflammatory diseases such as atherosclerosis, to host defence throughout the biological world, and are ancient in the context of life on earth, having originated more than 1 billion years ago: prior to the divergence of plants and animals. TIR domain receptors couple to at least two sets of well-characterized pathways: those leading to the activation of inhibitory κB kinase complexes/nuclear factor κB, and those leading to the activation of mitogen-activated protein kinase/AP-1/ATF-2 etc. We have been investigating these systems using a combination of expression screening methods to identify new components, and real-time green fluorescent protein-based techniques to observe execution of signalling programmes in real time. Our data reveal that there is a very large level of cell-to-cell variation in signal programme execution even in clonal populations and that at least one mechanism for dealing with this heterogeneity is the assembly of signal transduction components into large multiprotein complexes.


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