Taxifolin ameliorates iron overload-induced hepatocellular injury: Modulating PI3K/AKT and p38 MAPK signaling, inflammatory response, and hepatocellular regeneration

2020 ◽  
Vol 330 ◽  
pp. 109230 ◽  
Author(s):  
Samir A. Salama ◽  
Ahmed M. Kabel
Keyword(s):  
Inflammatory Response ◽  
Iron Overload ◽  
P38 Mapk ◽  
Mapk Signaling ◽  
Hepatocellular Injury ◽  
Hepatocellular Regeneration

scholarly journals TREM-2-p38 MAPK signaling regulates neuroinflammation during chronic cerebral hypoperfusion combined with diabetes mellitus

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Jiawei Zhang ◽  
Yu Liu ◽  
Yaling Zheng ◽  
Yan Luo ◽  
Yu Du ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Cognitive Impairment ◽  
Inflammatory Response ◽  
P38 Mapk ◽  
High Glucose ◽  
Mapk Signaling ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion

Abstract Background Diabetes mellitus (DM) and chronic cerebral hypoperfusion(CCH)are both risk factors for cognitive impairment. However, whether DM and CCH can synergistically promote cognitive impairment and the related pathological mechanisms remain unknown. Methods To investigate the effect of DM and CCH on cognitive function, rats fed with high-fat diet (HFD) and injected with low-dose streptozotocin (STZ) followed by bilateral common carotid artery occlusion (BCCAO) were induced to mimic DM and CCH in vivo and mouse BV2 microglial cells were exposed to hypoxia and/or high glucose to mimic CCH complicated with DM pathologies in vitro. To further explore the underlying mechanism, TREM-2-specific small interfering RNA and TREM-2 overexpression lentivirus were used to knock out and overexpress TREM-2, respectively. Results Cognitive deficits, neuronal cell death, neuroinflammation with microglial activation, and TREM-2-MAPK signaling were enhanced when DM was superimposed on CCH both in vivo and in vitro. Manipulating TREM-2 expression levels markedly regulated the p38 MAPK signaling and the inflammatory response in vitro. TREM-2 knockout intensified while TREM-2 overexpression suppressed the p38 MAPK signaling and subsequent pro-inflammatory mediator production under high glucose and hypoxia condition. Conclusions These results suggest that TREM-2 negatively regulates p38 MAPK-mediated inflammatory response when DM was synergistically superimposed on CCH and highlight the importance of TREM-2 as a potential target of immune regulation in DM and CCH.

Sex differences in the myocardial inflammatory response to ischemia-reperfusion injury

2005 ◽  
Vol 288 (2) ◽  
pp. E321-E326 ◽  
Author(s):  
Meijing Wang ◽  
Lauren Baker ◽  
Ben M. Tsai ◽  
Kirstan K. Meldrum ◽  
Daniel R. Meldrum
Keyword(s):  
Sex Differences ◽  
Inflammatory Response ◽  
P38 Mapk ◽  
Myocardial Function ◽  
Contractile Function ◽  
Ischemia Reperfusion ◽  
Mapk Signaling ◽  
Left Ventricular ◽  
Rt Pcr ◽  
Tnf Α

The myocardium generates inflammatory mediators during ischemia-reperfusion (I/R), and these mediators contribute to cardiac functional depression and apoptosis. The great majority of these data have been derived from male animals and humans. Sex has a profound effect over many inflammatory responses; however, it is unknown whether sex affects the cardiac inflammatory response to acute myocardial I/R. We hypothesized the existence of inherent sex differences in myocardial function, expression of inflammatory cytokines, and activation of the p38 mitogen-activated protein kinase (MAPK) signaling pathway after I/R. Isolated rat hearts from age-matched adult males and females were perfused (Langendorff), and myocardial contractile function was continuously recorded. After I/R, myocardium was assessed for expression of TNF-α, IL-1β, and IL-6 (RT-PCR, ELISA); IL-1α and IL-10 mRNA (RT-PCR); and activation of p38 MAPK (Western blot). All indexes of postischemic myocardial function [left ventricular developed pressure, left ventricular end-diastolic pressure, and maximal positive (+dP/d t) and negative (−dP/d t) values of the first derivative of pressure] were significantly improved in females compared with males. Compared with males, females had decreased myocardial TNF-α, IL-1β, and IL-6 (mRNA, protein) and decreased activation of p38 MAPK pathway. These data demonstrate that hearts from age-matched adult females are relatively protected against I/R injury, possibly due to a diminished inflammatory response.

Renoprotective Effects of Alpha Lipoic Acid on Iron Overload-Induced Kidney Injury in Rats by Suppressing NADPH Oxidase 4 and p38 MAPK Signaling

2019 ◽  
Vol 193 (2) ◽  
pp. 483-493 ◽  
Author(s):  
Zahide Cavdar ◽  
Mehmet Asi Oktan ◽  
Cemre Ural ◽  
Meryem Calisir ◽  
Ayse Kocak ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Iron Overload ◽  
P38 Mapk ◽  
Lipoic Acid ◽  
Kidney Injury ◽  
Mapk Signaling ◽  
Alpha Lipoic Acid ◽  
Nadph Oxidase 4

scholarly journals Dachengqi Decoction Attenuates Inflammatory Response via Inhibiting HMGB1 Mediated NF-κB and P38 MAPK Signaling Pathways in Severe Acute Pancreatitis

2015 ◽  
Vol 37 (4) ◽  
pp. 1379-1389 ◽  
Author(s):  
Zhuoan Chen ◽  
Yafeng Chen ◽  
Liyun Pan ◽  
Hongchang Li ◽  
Jiamin Tu ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Inflammatory Response ◽  
P38 Mapk ◽  
Severe Acute Pancreatitis ◽  
Mapk Pathway ◽  
Mapk Signaling ◽  
Comprehensive Treatment ◽  
High Dose ◽  
Dependent Manner ◽  
Dachengqi Decoction

Background/Aims: Severe acute pancreatitis (SAP) is a sudden inflammation of the pancreas. The traditional Chinese medicine formula Dachengqi decoction (DCQD) is proven to be beneficial in the comprehensive treatment for pancreatitis patients in clinical practice. However, the molecular mechanism of DCQD on SAP remains unclear. High mobility group box 1(HMGB1) that functions as a damage-associated molecular pattern molecule (DAMP) has attracted much interest. Methods: In this study, we used lipopolysaccharide (LPS) and cerulein to induce severe acute pancreatitis in C57BL/6 mice with subsequent administration with low, medium and high dose (2.3 g/kg, 7 g/kg and 21 g/kg, respectively) of DCQD. Results: DCQD treatment improved the pathological score and decreased serum amylase and lipase in a dose-dependent manner. In addition, it suppressed the immune cell-induced secretion of HMGB1 and its translocation from the nucleus to the cytoplasm, thus repressing the expression of IL-6 and TNF-α. Further, pretreatment with DCQD decreased responses of TLRs, and suppressed the activation of NF-kB and p38 MAPK pathway. Conclusion: Decreasing the secretion of HMGB1 could reduce pro-inflammatory cytokines, which may help cutting down the risks of development from localized pathological changes to a systemic inflammatory response syndrome and even lead to multiple organ failure.

scholarly journals Genipin Ameliorates Carbon Tetrachloride-Induced Liver Injury in Mice via the Concomitant Inhibition of Inflammation and Induction of Autophagy

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Ya Wang ◽  
Tianming Zhao ◽  
You Deng ◽  
Lijun Hou ◽  
Xiaofei Fan ◽  
...  
Keyword(s):  
Carbon Tetrachloride ◽  
Liver Injury ◽  
Inflammatory Response ◽  
Protective Effect ◽  
P38 Mapk ◽  
Mapk Signaling ◽  
Autophagic Flux ◽  
Mice Model ◽  
Stat3 Signaling Pathway ◽  
Liver Changes

Genipin, as the most effective ingredient of various traditional medications, encompasses antioxidative, anti-inflammatory, and antibacterial capacities. More recently, it is suggested that genipin protects against septic liver damage by restoring autophagy. The purpose of the current study was to explore the protective effect of genipin against carbon tetrachloride- (CCl4-) induced acute liver injury (ALI) and its underlying molecular machinery. Our results indicated that treatment with genipin significantly reduced CCl4-induced hepatotoxicity by ameliorating histological liver changes, decreasing the aspartate aminotransferase and alanine transaminase levels, alleviating the secretion of inflammatory cytokines, and promoting autophagic flux. Moreover, genipin effectively induced the conversion of LC3 and inhibition of p62 accumulation. The liver expressions of ATG5, ATG7, and ATG12 were significantly increased by genipin pretreatment in the ALI mice model. This protective effect may be mediated by the inhibition of mTOR and the activation of p38 MAPK signaling pathways. Meanwhile, genipin attenuated CCl4-induced inflammatory response by inhibiting the NF-κB and STAT3 signaling pathway. In addition, pretreatment with autophagy inhibitor 3-methyladenine (3-MA) or inhibition of p38 MAPK by SB203580 abolished the hepatoprotective effect of genipin. Taken together, our study implicates that genipin has a protective potential against CCl4-induced hepatotoxicity, which might be strongly associated with the induction of autophagy and the attenuation of inflammatory response.

IL-8 amplifies CD40/CD154-mediated ICAM-1 production via the CXCR-1 receptor and p38-MAPK pathway in human renal proximal tubule cells

2009 ◽  
Vol 296 (2) ◽  
pp. F438-F445 ◽  
Author(s):  
Hongye Li ◽  
Edward P. Nord
Keyword(s):  
Protein Kinase ◽  
Inflammatory Response ◽  
Proximal Tubule ◽  
P38 Mapk ◽  
Mapk Pathway ◽  
Primary Cultures ◽  
Mapk Signaling ◽  
Intercellular Adhesion Molecule ◽  
Proximal Tubule Cells ◽  
Tubule Cells

Activation of the CD40 receptor by its cognate ligand, CD154, results in interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) production and increased intercellular adhesion molecule-1 (ICAM-1) expression in proximal tubule cells (PTCs). The independent role of these two proinflammatory chemokines, IL-8 and MCP-1, in inciting an inflammatory response in PTCs was explored. Exposure of primary cultures of human renal PTCs to recombinant IL-8 and MCP-1 resulted in increased ICAM-1 expression measured by quantitative real-time PCR, but confirmed only for IL-8 by immunoblot. The mechanism of action of IL-8 was explored in further detail. Immunohistochemistry identified both the CXCR-1 and CXCR-2 receptors, confirmed by RT-PCR, immunoprecipitation, immunoblot, and FACS analysis. IL-8 increased ICAM-1 expression only via the CXCR-1 receptor, which in turn resulted in activation of the p38 mitogen-activated protein kinase (MAPK) pathway; neither the extracellular signal-related kinase (ERK) 1/2 MAPK pathway nor the stress-activated protein kinase (SAPK)/c-Jun NH2 terminal kinase (JNK) pathway was involved. CD154/CD40-mediated ICAM-1 upregulation was not affected by preincubation of monolayers with the CXCR-1 blocking antibody, indicating that ICAM-1 expression occurs independent of CD154-mediated IL-8 production. Coincubation of monolayers with both CD154 and IL-8 resulted in a greater ICAM-1 response than either compound alone. We conclude that in human renal PTCs, IL-8 upregulates ICAM-1 production by engaging the CXCR-1 receptor and p38 MAPK signaling pathway. This cascade of events is independent of CD40/CD154-mediated IL-8 stimulation and ICAM-1 production and serves to amplify the inflammatory response.

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