Inhibitors Of The Janus Kinase – Signal Transducers And Activators Of Transcription ( Jak/ Stat) Signaling Pathway

2000 ◽  
Author(s):  
Robyn Starr
Keyword(s):  
Signaling Pathway ◽  
Janus Kinase ◽  
Signal Transducers ◽  
Stat Signaling ◽  
Signal Transducers And Activators

scholarly journals Alterations in Janus Kinase (JAK)-Signal Transducers and Activators of Transcription (STAT) Signaling in Patients With End-Stage Dilated Cardiomyopathy

Circulation ◽  
2003 ◽  
Vol 107 (6) ◽  
pp. 798-802 ◽  
Author(s):  
Edith K. Podewski ◽  
Denise Hilfiker-Kleiner ◽  
Andres Hilfiker ◽  
Henning Morawietz ◽  
Artur Lichtenberg ◽  
...  
Keyword(s):  
Dilated Cardiomyopathy ◽  
Janus Kinase ◽  
Signal Transducers ◽  
Stat Signaling ◽  
End Stage ◽  
Signal Transducers And Activators

Liraglutide Exerts Potential Anti-inflammatory Effect in Type 1 Diabetes by Inhibiting IFN-γ Production via Suppressing JAK-STAT Pathway

2019 ◽  
Vol 19 (5) ◽  
pp. 656-664
Author(s):  
Yunjuan Zhao ◽  
Yunliang Xie ◽  
Wangen Li
Keyword(s):  
Type 1 Diabetes ◽  
Signaling Pathway ◽  
Interferon Γ ◽  
Janus Kinase ◽  
Janus Kinase 2 ◽  
Signal Transducers ◽  
High Glucose Condition ◽  
Glucose Condition ◽  
Signal Transducers And Activators

Background: Type 1 diabetes is a T cell-mediated autoimmune disease. Interferon γ plays a critical role in the pathogenesis of type 1 diabetes. Signal transducer and activator of transcription transduces type I interferon cytokines in T cells, leading to Th1 cell differentiation and production of interferon γ. Recent studies suggest that liraglutide reduces the plasma concentration of C-reative protein in patients with type 1 diabetes and protects β cell function in the non-obese diabetic mouse. Objective: The study aimed to explore the effect of glucagon-like peptide-1 analogue on interferon γ production and the underlying signaling pathway in vitro. Methods: Jurkat E6-1 cells were intervened with different concentrations of glucose and liraglutide during different time periods. Protein was extracted from Jurkat E6-1 cells. The target proteins (total and activated Janus kinase 2, signal transducers and activators of transcription 4 and interferon γ) were detected by Western blot. Results: Glucose stimulates interferon γ expression and activates Janus kinase 2/signal transducers and activators of transcription 4 signaling pathway in Jurkat E6-1 cells in a concentration and timedependent manner. Under high glucose condition, liraglutide inhibits interferon γ expression and Janus kinase 2/signal transducers and activators of transcription 4 signaling pathway in Jurkat E6-1 cells in a concentration and time-dependent manner. The Janus kinase responsible for liraglutide-inhibited signal transducers and activators of transcription 4 phosphorylation is Janus kinase 2, which is also required for the interferon γ induction. Finally, we demonstrated that under high glucose condition, liraglutide inhibits interferon γ expression via Janus kinase 2/signal transducers and activators of transcription 4 signaling pathway in Jurkat E6-1 cells. Conclusion: Liraglutide inhibits Jurkat E6-1 cells to produce interferon γ via the Janus kinase/signal transducers and activators of transcription signaling pathway under high glucose condition, which implies its potential in the immunoregulatory effect of type 1 diabetes.

Therapeutic potential of JAK/STAT pathway modulation in mood disorders

2018 ◽  
Vol 30 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Aisha S. Shariq ◽  
Elisa Brietzke ◽  
Joshua D. Rosenblat ◽  
Zihang Pan ◽  
Carola Rong ◽  
...  
Keyword(s):  
Mood Disorders ◽  
Signaling Pathway ◽  
Depressive Disorders ◽  
Therapeutic Potential ◽  
Indirect Evidence ◽  
Janus Kinase ◽  
Low Grade ◽  
Signal Transducers ◽  
Inflammatory Conditions ◽  
Stat Signaling

Abstract Convergent evidence demonstrates that immune dysfunction (e.g. chronic low-grade inflammatory activation) plays an important role in the development and progression of mood disorders. The Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway is a pleiotropic cellular cascade that transduces numerous signals, including signals from the release of cytokines and growth factors. The JAK/STAT signaling pathway is involved in mediating several functions of the central nervous system, including neurogenesis, synaptic plasticity, gliogenesis, and microglial activation, all of which have been implicated in the pathophysiology of mood disorders. In addition, the antidepressant actions of current treatments have been shown to be mediated by JAK/STAT-dependent mechanisms. To date, two JAK inhibitors (JAKinibs) have been approved by the U.S. Food and Drug Administration and are primarily indicated for the treatment of inflammatory conditions such as rheumatoid arthritis. Indirect evidence from studies in populations with inflammatory conditions indicates that JAKinibs significantly improve measures of mood and quality of life. There is also direct evidence from studies in populations with depressive disorders, suggesting that JAK/STAT pathways may be involved in the pathophysiology of depression and that the inhibition of specific JAK/STAT pathways (i.e. via JAKinibs) may be a promising novel treatment for depressive disorders.

Constitutive activation of STAT-3 and downregulation of SOCS-3 expression induced by adrenalectomy

2001 ◽  
Vol 281 (6) ◽  
pp. R2048-R2058 ◽  
Author(s):  
Abram M. Madiehe ◽  
Ling Lin ◽  
Christy White ◽  
H. Doug Braymer ◽  
George A. Bray ◽  
...  
Keyword(s):  
Dna Binding ◽  
Signaling Pathway ◽  
Leptin Receptor ◽  
Binding Activity ◽  
Janus Kinase ◽  
Adrenal Steroids ◽  
Western Blots ◽  
Protein Levels ◽  
Dna Binding Activity ◽  
Stat Signaling

Removal of adrenal steroids by adrenalectomy (ADX) slows or reverses the development of many forms of obesity in rodents, including those that are leptin or leptin receptor deficient. Obesity is associated with hyperleptinemia and leptin resistance. We hypothesized that glucocorticoids impair leptin receptor signaling and that removal thereof would activate the Janus kinase (JAK)-signal transducers and activators of transcription (STAT) signaling pathway. The inhibitory effect of leptin (2.5 μg icv) on food intake was enhanced in ADX rats. A combination of ribonuclease protection assays, RT-PCR, Western blots, and mobility shift assays was used to evaluate the leptin signaling pathway in whole hypothalami from sham-operated, ADX and corticosterone-replaced ADX (ADX-R) Sprague-Dawley rats that were treated acutely with either saline vehicle or leptin intracerebroventricularly. ADX increased the expression of leptin receptor mRNA, increased STAT-3 mRNA and protein levels, induced constitutive STAT-3 phosphorylation and DNA binding activity, and also reduced suppressor of cytokine signaling-3 (SOCS-3) mRNA and protein levels. ADX and leptin treatment increased STAT-3 phosphorylation, but with no concomitant increase in DNA binding activity. Leptin and ADX decreased NPY mRNA expression, but their combination did not further decrease NPY mRNA. Corticosterone supplementation of ADX rats partially reversed many of these effects. In conclusion, ADX through activation of STAT-3 and inhibition of SOCS-3 activates the JAK-STAT signaling pathway. These effects most probably explain the ability to prevent the development of obesity by removal of adrenal steroids.

Sign in / Sign up

Export Citation Format

Share Document