Fred Schaper’s research while affiliated with Otto-von-Guericke University Magdeburg and other places

What is this page?


This page lists works of an author who doesn't have a ResearchGate profile or hasn't added the works to their profile yet. It is automatically generated from public (personal) data to further our legitimate goal of comprehensive and accurate scientific recordkeeping. If you are this author and want this page removed, please let us know.

Publications (142)


STAT3 negatively regulates REDD1 mRNA expression. (A) Domain structure of STAT3 WT. CCD, coiled‐coil domain; DBD, DNA‐binding domain; LD, linker domain; NTD, N‐terminal domain; SH2, Src homology domain; TAD, transactivation domain. (B, C) HepG2 (B) and MEF STAT3fl/fl cells (C) were stimulated with 10 ng·mL⁻¹ IL‐6 or Hy‐IL‐6, respectively, for 60 min. For control, cells were left untreated. RNA was isolated and transcribed into cDNA. REDD1 mRNA was quantified by qRT‐PCR. Maximal mRNA expression was set to 100%. Data are given as mean from n = 3 independent experiments ± SD. Repeated measures ANOVA, **P < 0.01. (D) MEF STAT3fl/fl, MEF STAT3−/− and MEF STAT3 WT cells were stimulated with 10 ng·mL⁻¹ Hy‐IL‐6 for 15 min. STAT3 Y705 phosphorylation, ERK1/2 phosphorylation, STAT3, ERK and tubulin expression were evaluated by western blotting. Tubulin serves as the loading control. A representative result of n = 3 independent experiments is shown. (E) RNA from MEF STAT3fl/fl, MEF STAT3−/− and MEF STAT3 WT cells was isolated and transcribed into cDNA. REDD1 mRNA was quantified by qRT‐PCR. Maximal mRNA expression was set to 100%. Data are given as mean from n = 3 independent experiments ± SD. Repeated measures ANOVA, ***P < 0.001, **P < 0.01. (F) MEF STAT3fl/fl, MEF STAT3−/− and MEF STAT3 WT cells were seeded for 24 h on poly‐L‐lysine‐coated cover slides. Cells fixed with methanol were stained overnight with primary antibodies against STAT3. After washing, cells were stained with PE‐coupled secondary antibodies, and the subcellular distribution of STAT3 was analysed by confocal microscopy. Control cells were either left unstained or stained with secondary antibodies. Representative cells are shown. Scale bars represent 10 μm. DIC, differential interference contrast.
Phosphorylation of STAT3 at Y705 is crucial for the reduction of REDD1 mRNA and protein expression. (A) Domain structure of STAT3 Y705F. (B) STAT3 expression in MEF STAT3−/− cells and MEF STAT3 Y705F cells was evaluated by intracellular flow cytometry using a specific fluorescent antibody against STAT3. (C) MEF STAT3 Y705F cells were seeded for 24 h on poly‐L‐lysine‐coated cover slides. Cells fixed with methanol were stained overnight with primary antibodies against STAT3. After washing, cells were stained with PE‐coupled secondary antibodies, and the subcellular distribution of STAT3 was analysed by confocal microscopy. For control, cells were either left unstained or stained with secondary antibodies. Representative cells are shown. Scale bars represent 10 μm. DIC: differential interference contrast. (D) MEF STAT3fl/fl, MEF STAT3−/−, MEF STAT3 WT and MEF STAT3 Y705F cells were stimulated with 10 ng·mL⁻¹ Hy‐IL‐6 for 15 min. STAT3 Y705 phosphorylation, STAT3 and tubulin expression were evaluated by western blotting. Tubulin serves as the loading control. A representative result of n = 3 independent experiments is shown. (E, F) MEF STAT3fl/fl, MEF STAT3−/−, MEF STAT3 WT and MEF STAT3 Y705F cells were stimulated with 10 ng·mL⁻¹ Hy‐IL‐6 for 60 min (E) or left untreated (F). RNA was isolated and transcribed into cDNA. SOCS3 mRNA (E) and REDD1 mRNA (F) were quantified by qRT‐PCR. Maximal mRNA expression was set to 100%. Data are given as mean from n = 3 independent experiments ± SD. (G) MEF STAT3fl/fl, MEF STAT3−/−, MEF STAT3 WT and MEF STAT3 Y705F cells were lysed and REDD1 and STAT3 expression were evaluated by western blotting. Tubulin serves as the loading control. A representative result of n = 3 independent experiments is shown. (H) Immunoblots from three independent experiments were quantified using image studio lite 4.0 software. Expression of REDD1 in MEF STAT3−/− cells was set to 100%. Data are given as mean from n = 3 independent experiments ± SD. Repeated measures ANOVA, ***P < 0.001, *P < 0.05.
Phosphorylation of STAT3 at S727 is not necessary for the reduction of REDD1 mRNA and protein expression. (A) Domain structure of STAT3 S727A. (B) STAT3 expression in MEF STAT3−/− and MEF STAT3 S727A cells was evaluated by intracellular flow cytometry using a specific fluorescent antibody against STAT3. (C) MEF STAT3 S727A cells were seeded for 24 h on poly‐L‐lysine‐coated cover slides. Cells fixed with methanol were stained overnight with primary antibodies against STAT3. After washing, cells were stained with PE‐coupled secondary antibodies, and the subcellular distribution of STAT3 was analysed by confocal microscopy. Control cells were either left unstained or stained with secondary antibodies. Representative cells are shown. Scale bars represent 10 μm. DIC, differential interference contrast. (D) MEF STAT3fl/fl, MEF STAT3−/−, MEF STAT3 WT and MEF STAT3 S727A were stimulated with 10 ng·mL⁻¹ Hy‐IL‐6 for 15 min. STAT3 Y705 phosphorylation, STAT3 S727 phosphorylation, STAT3 and tubulin expression were evaluated by western blotting. Tubulin serves as the loading control. A representative result of n = 3 independent experiments is shown. (E, F) MEF STAT3fl/fl, MEF STAT3−/−, MEF STAT3 WT and MEF STAT3 S727A cells were stimulated with 10 ng·mL⁻¹ Hy‐IL‐6 for 60 min (E) or left untreated (F). RNA was isolated and transcribed into cDNA. SOCS3 mRNA (E) and REDD1 mRNA (F) were quantified by qRT‐PCR. Maximal mRNA expression was set to 100%. Data are given as mean from n = 3 independent experiments ± SD. (G) MEF STAT3fl/fl, MEF STAT3−/−, MEF STAT3 WT and MEF STAT3 S727A cells were lysed and REDD1 and STAT3 expression were evaluated by western blotting. Tubulin serves as the loading control. A representative result of n = 3 independent experiments is shown. (H) Immunoblots from three independent experiments were quantified using image studio lite 4.0 software. Expression of REDD1 in MEF STAT3−/− cells was set to 100%. Data are given as mean from n = 3 independent experiments ± SD. Repeated measures ANOVA, ***P < 0.001, **P < 0.01.
Phosphorylation of STAT3 at S727 contributes to STAT3 Y705‐dependent reduction of REDD1 mRNA expression. (A) Domain structure of STAT3 Y705F/S727A. (B) STAT3 expression in MEF STAT3−/− and MEF STAT3 Y705F/S727A cells was evaluated by intracellular flow cytometry using a specific fluorescent antibody against STAT3. (C) MEF STAT3 Y705F/S727A cells were seeded for 24 h on poly‐L‐lysine‐coated cover slides. Cells fixed with methanol were stained overnight with primary antibodies against STAT3. After washing, cells were stained with PE‐coupled secondary antibodies, and the subcellular distribution of STAT3 was analysed by confocal microscopy. Control cells were either left unstained or stained with secondary antibodies. Representative cells are shown. Scale bars represent 10 μm. DIC, differential interference contrast. (D) MEF STAT3fl/fl, MEF STAT3−/−, MEF STAT3 WT and MEF STAT3 Y705F/S727A cells were stimulated with 10 ng·mL⁻¹ Hy‐IL‐6 for 15 min. STAT3 Y705 phosphorylation, STAT3 S727 phosphorylation, STAT3 and tubulin expression were evaluated by western blotting. Tubulin serves as the loading control. A representative result of n = 3 independent experiments is shown. (E, F) MEF STAT3fl/fl, MEF STAT3−/−, MEF STAT3 WT and MEF STAT3 Y705F/S727A cells were stimulated with 10 ng·mL⁻¹ Hy‐IL‐6 for 60 min (E) or left untreated (F). SOCS3 mRNA (D) and REDD1 mRNA (E) expression were quantified by qRT‐PCR. Maximal mRNA expression was set to 100%. Data are given as mean from n = 3 independent experiments ± SD. (G) MEF STAT3fl/fl, MEF STAT3−/−, MEF STAT3 WT and MEF STAT3 Y705F/S727A cells were lysed and REDD1 and STAT3 expression were evaluated by western blotting. Tubulin serves as the loading control. A representative result of n = 3 independent experiments is shown. (H) Immunoblots from three independent experiments were quantified using image studio lite 4.0 software. Expression of REDD1 in MEF STAT3−/− cells was set to 100%. Data are given as mean from n = 3 independent experiments ± SD. Repeated measures ANOVA, ***P < 0.001, **P < 0.01, *P < 0.05.
STAT3 binds to REDD1 promoter elements. (A–D) MEF STAT3fl/fl (A, C) and STAT3−/− (B, D) cells were transfected with human SOCS3 (A, B) or human REDD1 (C, D) promoter–reporter constructs and a β‐galactosidase‐encoding expression vector. Cells were treated for 16 h with Hy‐IL‐6 (10 ng·mL⁻¹). Luciferase activity was normalized to β‐galactosidase activity. Maximal reporter activity was set to 100%. Data are given as a mean of n = 3 independent experiments ± SD. Repeated measures ANOVA, ***P < 0.001. (E) HepG2 cells were stimulated for 60 min with 10 ng·mL⁻¹ IL‐6. DNA and proteins were cross‐linked and digested enzymatically. Immunoprecipitation was performed with anti‐STAT3 and anti‐IgG antibodies coupled to magnetic beads. Precipitated DNA was analysed by qRT‐PCR. Fold enrichment was calculated by: 2−Ctsample−CtIgG. Data are given as a mean of n = 3 independent experiments ± SD. (F) Alignment of potential STAT3‐binding sides in human (NC_000010.11) and murine REDD1 (NC_000076.7) promoters. Capital letters indicate sequence homologies. Human and murine STAT3 consensus DNA‐binding sites from JASPAR database [51].

+3

Non‐canonical STAT3 function reduces REDD1 transcription
  • Article
  • Full-text available

December 2022

·

33 Reads

·

4 Citations

·

Nicole Wundrack

·

Svenja Schulz

·

[...]

·

The transcription factor STAT3 is a potent activator of transcription, but evidence exists that STAT3 can also repress gene expression. However, little is known about the molecular mechanisms involved in STAT3‐dependent gene repression. Notably, STAT3 reduces the expression of the stress‐induced mTOR inhibitor REDD1 by reducing REDD1 mRNA transcription. Here, we determined the functional domains of STAT3 responsible for the reduction of REDD1 mRNA and protein expression. Within STAT3, the N‐terminal domain and tyrosine 705 are crucial for STAT3‐dependent reduction of REDD1 expression. Interestingly, binding of STAT3 to canonical STAT‐binding sides within the REDD1 promoter is not necessary for STAT3‐mediated reduction of REDD1 expression. Still, STAT3 is recruited to the REDD1 promoter upon stimulation with IL‐6, and reduces REDD1 promoter activity. The reduction of REDD1 expression is specific for STAT3, as neither expression nor activation of STAT1 reduces REDD1 mRNA and protein expression. In summary, we present a novel, non‐canonical STAT3‐dependent mechanism for reducing gene expression. This transcriptional repression increases the functions of STAT3 proteins beyond classical transcriptional activation of cytokine‐regulated target genes to a more complex function in modulating gene expression in immunity and cellular stress.

Download

Mediatoren

October 2022

·

9 Reads

Im vorangegangenen ► Kap. 33 wurden die Prinzipien zellulärer Kommunikation beschrieben. In diesem und im folgenden Kapitel werden die extrazellulären Mediatoren (Kap. 34) sowie Rezeptoren und ihre Signaltransduktion (► Kap. 35) im Detail besprochen. Extrazelluläre Signalmoleküle spielen eine entscheidende Rolle bei der Kommunikation zwischen Zellen und Organen. Störungen dieser Kommunikation führen zu klinisch oft gut definierten Krankheitsbildern. In verstärktem Maße werden vor allem akute und chronisch-entzündliche Erkrankungen als Konsequenzen einer gestörten Regulation durch Cytokine verstanden, sodass speziell diesen Signalmolekülen eine zunehmende klinische Bedeutung zukommt.




All-in-one superparamagnetic and SERS-active niosomes for dual-targeted in vitro detection of breast cancer cells

March 2022

·

47 Reads

·

9 Citations

In vitro and in vivo biosensing through surface-enhanced Raman scattering often suffer from signal contamination diminishing both the limit of detection and quantification. However, overcoming the lack of specificity requires excessive nanoparticle concentrations, which may lead to adverse side effects if applied to patients. In this study we propose encapsulation of iron oxide (FexOy) and gold (Au) nanoparticles (NPs) into the bilayer structure of transferrin-modified niosomes. This approach enables achieving greatly enhanced and contamination-free SERS-signals in vitro as well as a dual-targeting functionality towards MCF-7 breast cancer cells. An in-depth characterization of FexOyNPs- and AuNPs-loaded niosomes (AuNPs/FexOyNPs/NIO) after magnetic downstream processing reveals defined hybrid niosome structures, which show a long-term SERS-signal stability in various media such as MCF-7 cell culture medium. In vitro 2D-SERS imaging unveil a successful incorporation of a non-toxic dose of hybrid NPs into MCF-7 cells, which leads to strong and almost contamination-free SERS-signals. The measured signal-to-noise ratio of the in vitro signal exceeds the values required by DIN 32645 for the successful validation of a detection method. The hybrid niosomes can thus be considered a promising and efficient agent for the establishment and commercialization of a highly sensitive detection kit for monitoring cancerous tissue.


The tyrosine phosphatase SHP2 increases robustness and information transfer within IL-6-induced JAK/STAT signalling

December 2021

·

83 Reads

·

31 Citations

Cell Communication and Signaling

Background Cell-to-cell heterogeneity is an inherent feature of multicellular organisms and is central in all physiological and pathophysiological processes including cellular signal transduction. The cytokine IL-6 is an essential mediator of pro- and anti-inflammatory processes. Dysregulated IL-6-induced intracellular JAK/STAT signalling is associated with severe inflammatory and proliferative diseases. Under physiological conditions JAK/STAT signalling is rigorously controlled and timely orchestrated by regulatory mechanisms such as expression of the feedback-inhibitor SOCS3 and activation of the protein-tyrosine phosphatase SHP2 (PTPN11). Interestingly, the function of negative regulators seems not to be restricted to controlling the strength and timely orchestration of IL-6-induced STAT3 activation. Exemplarily, SOCS3 increases robustness of late IL-6-induced STAT3 activation against heterogenous STAT3 expression and reduces the amount of information transferred through JAK/STAT signalling. Methods Here we use multiplexed single-cell analyses and information theoretic approaches to clarify whether also SHP2 contributes to robustness of STAT3 activation and whether SHP2 affects the amount of information transferred through IL-6-induced JAK/STAT signalling. Results SHP2 increases robustness of both basal, cytokine-independent STAT3 activation and early IL-6-induced STAT3 activation against differential STAT3 expression. However, SHP2 does not affect robustness of late IL-6-induced STAT3 activation. In contrast to SOCS3, SHP2 increases the amount of information transferred through IL-6-induced JAK/STAT signalling, probably by reducing cytokine-independent STAT3 activation and thereby increasing sensitivity of the cells. These effects are independent of SHP2-dependent MAPK activation. Conclusion In summary, the results of this study extend our knowledge of the functions of SHP2 in IL-6-induced JAK/STAT signalling. SHP2 is not only a repressor of basal and cytokine-induced STAT3 activity, but also ensures robustness and transmission of information. Plain English summary Cells within a multicellular organism communicate with each other to exchange information about the environment. Communication between cells is facilitated by soluble molecules that transmit information from one cell to the other. Cytokines such as interleukin-6 are important soluble mediators that are secreted when an organism is faced with infections or inflammation. Secreted cytokines bind to receptors within the membrane of their target cells. This binding induces activation of an intracellular cascade of reactions called signal transduction, which leads to cellular responses. An important example of intracellular signal transduction is JAK/STAT signalling. In healthy organisms signalling is controlled and timed by regulatory mechanisms, whose activation results in a controlled shutdown of signalling pathways. Interestingly, not all cells within an organism are identical. They differ in the amount of proteins involved in signal transduction, such as STAT3. These differences shape cellular communication and responses to intracellular signalling. Here, we show that an important negative regulatory protein called SHP2 (or PTPN11) is not only responsible for shutting down signalling, but also for steering signalling in heterogeneous cell populations. SHP2 increases robustness of STAT3 activation against variable STAT3 amounts in individual cells. Additionally, it increases the amount of information transferred through JAK/STAT signalling by increasing the dynamic range of pathway activation in heterogeneous cell populations. This is an amazing new function of negative regulatory proteins that contributes to communication in heterogeneous multicellular organisms in health and disease.


Figure 3
Figure 6
Figure 8
Figure 9
Figure 10
All-in-one Superparamagnetic and SERS-active Niosomes for Dual-targeted in Vitro Detection of Breast Cancer Cells

November 2021

·

92 Reads

Background In vitro and in vivo biosensing through surface-enhanced Raman scattering often suffer from signal contamination diminishing both the limit of detection and quantification. However, overcoming the lack of specificity requires excessive nanoparticle concentrations, which may lead to adverse side effects if applied to patients. ResultsWe propose encapsulation of iron oxide (Fe x O y ) and gold (Au) nanoparticles (NPs) into the bilayer structure of transferrin-modified niosomes. This approach enables achieving greatly enhanced and contamination-free SERS-signals in vitro as well as a dual-targeting functionality towards MCF-7 breast cancer cells. An in-depth characterization of Fe x O y NPs- and AuNPs-loaded niosomes (AuNPs/Fe x O y NPs/NIO) after magnetic downstream processing reveals defined hybrid niosome structures, which show a long-term SERS-signal stability in various media such as MCF-7 cell culture medium. In vitro 2D-SERS imaging unveil a successful incorporation of a non-toxic dose of hybrid NPs into MCF-7 cells, which leads to strong and almost contamination-free SERS-signals. The measured signal-to-noise ratio of the in vitro signal exceeds the values required by DIN 32645 for the successful validation of a detection method. Conclusions The hybrid niosomes can be considered a promising and efficient agent for the establishment and commercialization of a highly sensitive detection kit for monitoring cancerous tissue.


Glucocorticoids attenuate interleukin‐6‐induced c‐Fos and Egr1 expression and impair neuritogenesis in PC12 cells

February 2021

·

60 Reads

·

7 Citations

Interleukin‐6 (IL‐6) is a cytokine primarily known for immune regulation. There is also growing evidence that IL‐6 triggers neurogenesis and impacts neural development, both life‐long occurring processes that can be impaired by early‐life and adult stress. Stress induces the release of glucocorticoids by activation of the hypothalamic–pituitary–adrenal (HPA) axis. On the cellular level, glucocorticoids act via the ubiquitously expressed glucocorticoid receptor. Thus, we aimed to elucidate whether glucocorticoids affect IL‐6‐induced neural development. Here, we show that IL‐6 signalling induces neurite outgrowth in adrenal pheochromocytoma PC12 cells in a mitogen‐activated protein kinase (MAPK) pathway‐dependent manner, since neurite outgrowth was diminished upon Mek‐inhibitor treatment. Using quantitative biochemical approaches, such as qRT‐PCR analysis of Hyper‐IL‐6 treated PC12 cells, we show that neurite outgrowth induced by IL‐6 signalling is accompanied by early and transient MAPK‐dependent mRNA expression of immediate early genes coding for proteins such as early growth response protein 1 (Egr1) and c‐Fos. This correlates with reduced proliferation and prolonged G0/G1 cell cycle arrest as determined by monitoring the cellular DNA content using flow cytometry. These results indicate for IL‐6 signalling‐induced neural differentiation. Interestingly, the glucocorticoid Dexamethasone impairs early IL‐6 signalling‐induced mRNA expression of c‐Fos and Egr1 and restrains neurite outgrowth. Impaired Egr1 and c‐Fos expression in neural development is implicated in the aetiology of neuropathologies. Thus, it appears likely that stress‐induced release of glucocorticoids, as well as therapeutically administered glucocorticoids, contribute to the development of neuropathologies by reducing the expression of Egr1 and c‐Fos, and by restraining IL‐6‐dependent neural differentiation. image


The multi-site docking protein Grb2-associated binder 1 (Gab1) enhances interleukin-6-induced MAPK-pathway activation in an SHP2-, Grb2-, and time-dependent manner

December 2019

·

49 Reads

·

23 Citations

Cell Communication and Signaling

Background: Cytokine-dependent activation of signalling pathways is tightly orchestrated. The spatiotemporal activation of signalling pathways dictates the specific physiological responses to cytokines. Dysregulated signalling accounts for neoplastic, developmental, and inflammatory diseases. Grb2-associated binder (Gab) family proteins are multi-site docking proteins, which expand cytokine-induced signal transduction in a spatial- and time-dependent manner by coordinating the recruitment of proteins involved in mitogen activated protein kinase (MAPK)/extracellular-signal regulated kinase (ERK) and phosphatidyl-inositol-3-kinase (PI3K) signalling. Interaction of Gab family proteins with these signalling proteins determines strength, duration and localization of active signalling cascades. However, the underlying molecular mechanisms of signal orchestration by Gab family proteins in IL-6-induced signalling are only scarcely understood. Methods: We performed kinetic analyses of interleukin-6 (IL-6)-induced MAPK activation and analysed downstream responses. We compared signalling in wild-type cells, Gab1 knock-out cells, those reconstituted to express Gab1 mutants, and cells expressing gp130 receptors or receptor mutants. Results: Interleukin-6-induced MAPK pathway activation can be sub-divided into an early Gab1-independent and a subsequent Gab1-dependent phase. Early Gab1-independent MAPK activation is critical for the subsequent initiation of Gab1-dependent amplification of MAPK pathway activation and requires binding of SH2 domain-containing phosphatase 2 (SHP2) to the interleukin-6 receptor complex. Subsequent and coordinated recruitment of Grb2 and SHP2 to Gab1 is essential for Gab1-dependent amplification of IL-6-induced late MAPK pathway activation and subsequent gene expression. Conclusions: Overall, we elaborated the molecular requirements for Gab1-dependent, spatiotemporal orchestration of interleukin-6-dependent MAPK signalling. We discriminated IL-6-induced Gab1-independent, early activation of MAPK signalling and Gab1-dependent, sustained activation of MAPK signalling.


Intragenic regulation of SOCS3 isoforms

December 2019

·

56 Reads

·

10 Citations

Cell Communication and Signaling

Background: Inflammatory reactions are commonly affected by stress responses. Interleukin-6 signalling is part of the inflammatory response and is stringently regulated by the feedback inhibitor SOCS3 expressed in a short and long isoform. Here, we studied the inhibitory potential of the two SOCS3 isoforms. Furthermore, we analysed the regulation of SOCS3 isoform expression and the role of PKR stress kinase signalling in SOCS3 protein expression. Methods: We performed Western blotting, reporter assays, genetic analyses and manipulations for studying SOCS3 isoform expression and activation of signalling components involved in interleukin-6-induced and PKR-dependent signalling. Results: Interleukin-6-induced endogenous expression of both SOCS3 isoforms was found in distinct cell types. Forced expression of either the long or short SOCS3 isoform demonstrated equal inhibitory activity of each isoform and confirmed longer half-life of the short isoform. Study of intragenic regulation of SOCS3 isoform expression revealed that (i) the 5'-UTR of SOCS3 mRNA restrains specifically expression of the long SOCS3 isoform, (ii) expression of the long isoform restrains expression of the short isoform, and (iii) signalling through the stress kinase PKR does not impact on SOCS3 isoform ratio. Conclusions: Both SOCS3 isoforms show a similar potential for inhibiting interleukin-6 signalling but differ in their half-lives. Relative expression of the isoforms depends on intragenic elements yet is independent of PKR signalling.


Citations (60)


... Additionally, macrophage-specific deletion of STAT3 in vivo significantly decreased SETDB2 expression in macrophages. Our data that STAT3 increases SETDB2 expression to ultimately decrease inflammatory gene expression are consistent with evidence from other labs that STAT3 can repress gene expression and provide another mechanism of the less-studied noncanonical function of STAT3 (36,37). ...

Reference:

The STAT3/SETDB2 axis dictates NF-κB-mediated inflammation in macrophages during wound repair
Non‐canonical STAT3 function reduces REDD1 transcription

... Encapsulating 5-thio-2-nitrobenzoic acid (TNB)functionalized AuNPs and superparamagnetic FexOyNPs simultaneously enables the production of magnetic and SERS-active nanoniosomes while maintaining their integrity. AuNPs/FexOyNPs/NIO/Tf presented numerous advantages, including optimal chemical stability, greater targeting efficiency, and remarkable SERS signal intensities, which makes hybrid niosomes an effective and promising agent in the development and commercialization of a highly sensitive cancer detection and treatment kit [136]. Barani exhibit exclusive properties such as biocompatibility, multivalency, reduced toxicity, and stability. ...

All-in-one superparamagnetic and SERS-active niosomes for dual-targeted in vitro detection of breast cancer cells

... 36 Because IL-6 is secreted by immune cells, it activates the JAK-STAT signaling pathway; the overactivation of this pathway can lead to aberrant inflammation via widespread cytokine release. 39 The JAK-STAT pathway represents a vital signaling conduit for myriad cytokines involved in physiological and pathological processes, including the cytokine storm. 40 In this pathway, the kinase JAK2 and its effector STAT3 represent key regulatory nodes because JAK2-mediated STAT3 phosphorylation facilitates its nuclear translocation and the transcriptional regulation of proinflammatory genes. ...

The tyrosine phosphatase SHP2 increases robustness and information transfer within IL-6-induced JAK/STAT signalling

Cell Communication and Signaling

... Moreover, ROS can trigger the activation of genes and nuclear proteins that function as transcription factors, such as c-Fos [94]. Additionally, a shift in the prooxidant-antioxidant balance caused by CSIS toward a prooxidant state also activates NF-κB, which induces the production of numerous genes involved in the activation of nitrosative and inflammatory mediators such as interleukin-6 (IL-6) [54], potentially triggering c-Fos expression at both mRNA and protein levels in the cells [95,96]. In line with this, increased protein expression of IL-6 has been revealed in chronically socially isolated rats [81,97]. ...

Glucocorticoids attenuate interleukin‐6‐induced c‐Fos and Egr1 expression and impair neuritogenesis in PC12 cells

... GRB2 Associated Binding Protein (Gab) family proteins are multisite docking proteins involved in the composition of GRB2. It is engaged in cytokine-induced signal transduction by regulating the recruitment of proteins involved in MAPK/ ERK and PI3K signaling [40]. It has been shown that Gab1 promotes ERK activation and participates in IL-22-mediated proliferation, migration, and differentiation of KCs [41]. ...

The multi-site docking protein Grb2-associated binder 1 (Gab1) enhances interleukin-6-induced MAPK-pathway activation in an SHP2-, Grb2-, and time-dependent manner

Cell Communication and Signaling

... Gene body methylation is generally linked to differential expression of gene isoforms 57 . SOCS3 has two cytokine-inducible isoforms (long and short) with varying expression levels ( Supplementary Fig. 5b), half-lives and stability 58 . As enhancers are known to regulate isoform expression and DNAm can influence enhancer activity, variable levels of methylation at this region might influence preferential expression of SOCS3 isoforms. ...

Intragenic regulation of SOCS3 isoforms

Cell Communication and Signaling

... Typically, these cells undergo parallel activation of both the classical and trans-signaling pathways. sIL-6R can competitively bind to IL-6 with mIL-6R, and the ratio of cell surface IL-6Ra/gp130 expression determines the strength of trans-signaling versus classical signal transduction (20). Moreover, when the molar concentration of sIL-6R exceeds that of IL-6, sgp130 can inhibit classical signal transduction (21). ...

Response to IL-6 trans- A nd IL-6 classic signalling is determined by the ratio of the IL-6 receptor α to gp130 expression: Fusing experimental insights and dynamic modelling

Cell Communication and Signaling

... The JAK-STAT1 pathway is an important signaling route in inflammatory macrophages for the secretion of cytokines that promote inflammation. Specifically, the conserved tyrosine and serine residues on the C-terminal domain of STAT1 are phosphorylated by JAK kinases and mitogen-activated protein kinases, respectively, which activate STAT1 [57]. This activation enables STAT1 to dimerize and translocate to the nucleus, where it regulates the expression of downstream chemokines, including CXCL9 and CXCL10. ...

Robustness and Information Transfer within IL-6-induced JAK/STAT Signalling

Communications Biology

... Cavin-1, found in caveolae, is an essential SOCS3-interacting protein with biological relevance. Loss of cavin-1 increases phosphorylation of cytokine-stimulated STAT3 and eliminates SOCS3-dependent IL-6 signaling inhibition by cAMP, demonstrating the importance of the interaction between cavin-1 and SOCS3 for SOCS3 functioning [43]. ...

Interaction of suppressor of cytokine signalling 3 with cavin-1 links SOCS3 function and cavin-1 stability

... However, IL-6 appears to be associated more directly with HO-1 gene activity. An IL-6-responsive element of the human HO-1 gene in liver cells and vascular endothelial cells has been indicated (Mitani et al., 1992;Lavrosky et al., 1996), consistent with subsequent evidence of HO-1 induction by IL-6 in human macrophages (Ricchetti et al., 2004), coronary endothelial cells (Deramaudt et al., 1999), corneal epithelial cells (Neil et al., 1995), and liver cells (Fukuda and Sassa, 1994;Tron et al., 2006), whereas the skin remains untested. ...

Regulation of Rat Heme Oxygenase–1 Gene Expression by Interleukin–6 via Jak/STAT Pathway
  • Citing Article
  • January 2005

Zeitschrift für Gastroenterologie