scholarly journals The ERK-p38MAPK-STAT3 Signalling Axis Regulates iNOS Expression and Salmonella Infection in Senescent Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Sheryl Erica Fernandes ◽  
Deepak Kumar Saini
Keyword(s):  
Nitric Oxide ◽  
Free Radical ◽  
Inflammatory Cytokines ◽  
Regulatory Network ◽  
Inos Expression ◽  
Salmonella Infection ◽  
Cellular Changes ◽  
Physiological Relevance ◽  
Stat3 Signalling ◽  
Pro Inflammatory Cytokines

The cellular changes occurring due to senescence like proliferation arrest, increase in free radical levels, and secretion of pro-inflammatory cytokines have been well studied, but its associated alteration in intracellular signalling networks has been scarcely explored. In this study, we examine the roles of three major kinases viz. p38 MAPK, ERK, and STAT3 in regulating iNOS expression and thereby the levels of the free radical Nitric oxide in senescent cells. Our study revealed that these kinases could differentially regulate iNOS in senescent cells compared to non-senescent cells. Further, we tested the physiological relevance of these alterations with Salmonella infection assays and established an inter-regulatory network between these kinases unique to infected senescent cells. Overall, our findings show how key signalling networks may be rewired in senescent cells rendering them phenotypically different.

scholarly journals Astilbe Chinensis ethanol extract suppresses inflammation in macrophages via NF-κB pathway

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Tae-Young Gil ◽  
Bo-Ram Jin ◽  
Chul-Hee Hong ◽  
Jong Hyuk Park ◽  
Hyo-Jin An
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Cytokines ◽  
Inflammatory Mediators ◽  
Ethanol Extract ◽  
Nuclear Factor Κb ◽  
Peritoneal Macrophages ◽  
Necrosis Factor Alpha ◽  
Iκb Kinase ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

Abstract Background Macrophages play a crucial role in inflammation. Astilbe chinensis is one of perennial herbs belonging to the genus Astilbe. Plants in the genus have been used for pain, headaches, arthralgia, and chronic bronchitis. However, the effect of A.chinensis on inflammation remains unclear. To study the anti-inflammatory action of A.chinensis ethanol extract (ACE), we investigated the effect of ACE on the production of pro-inflammatory mediators and cytokines in macrophages. Methods We evaluated the effectiveness of ACE in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and thioglycollate (TG)-elicited peritoneal macrophages from male C57BL/6 mice. We measured the levels of pro-inflammatory mediators and cytokines, and examined the anti-inflammatory actions of ACE on nuclear factor κB (NF-κB) pathway in the macrophages. Western blot analysis and immunofluorescence microscopy were used to determine protein level and translocation, respectively. Results ACE suppressed the output of nitric oxide (NO), prostaglandin E2 (PGE2), and pro-inflammatory cytokines in stimulated macrophages via inhibiting the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins. ACE suppressed mRNA expression of pro-inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α). We examined the efficacies of ACE on NF-κB activation by measuring the expressions including IκB kinase (IKK), inhibitor of κB (IκB), and nuclear p65 proteins. In addition, the inhibition of NF-κB p65’s translocation was determined with immunofluorescence assay. Conclusion Our findings manifested that ACE inhibited LPS or TG-induced inflammation by blocking the NF-κB signaling pathway in macrophages. It indicated that ACE is a potential therapeutic mean for inflammation and related diseases.

scholarly journals Depletion of iNOS-derived nitric oxide by prostaglandin H synthase-2 in inflammation-activated J774.2 macrophages through lipohydroperoxidase turnover

2005 ◽  
Vol 385 (3) ◽  
pp. 815-821 ◽  
Author(s):  
Stephen R. CLARK ◽  
Peter B. ANNING ◽  
Marcus J. COFFEY ◽  
Andrew G. ROBERTS ◽  
Lawrence J. MARNETT ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Cytokines ◽  
Mammalian Cells ◽  
Biological Effects ◽  
Interferon Γ ◽  
Dependent Manner ◽  
Prostaglandin H Synthase ◽  
Prostaglandin H ◽  
20 Nm ◽  
Pro Inflammatory Cytokines

PGHS-2 (prostaglandin H synthase-2) is induced in mammalian cells by pro-inflammatory cytokines in tandem with iNOS [high-output (‘inducible’) nitric oxide synthase], and is co-localized with iNOS and nitrotyrosine in human atheroma macrophages. Herein, murine J774.2 macrophages incubated with lipopolysaccharide and interferon γ showed induction of PGHS-2 and generated NO using iNOS that could be completely depleted by 12(S)-HPETE [12(S)-hydroperoxyeicosatetraenoic acid; 2.4 μM] or hydrogen peroxide (500 μM) (0.42±0.084 and 0.38±0.02 nmol·min−1·106 cells−1 for HPETE and H2O2 respectively). COS-7 cells transiently transfected with human PGHS-2 also showed HPETE- or H2O2-dependent NO decay (0.44±0.016 and 0.20±0.04 nmol·min−1·106 cells−1 for 2.4 μM HPETE and 500 μM H2O2 respectively). Finally, purified PGHS-2 consumed NO in the presence of HPETE or H2O2 (168 and 140 μM·min−1·μM enzyme−1 for HPETE and H2O2 respectively), in a haem-dependent manner, with 20 nM enzyme consuming up to 4 μM NO. Km (app) values for NO and 15(S)-HPETE were 1.7±0.2 and 0.45±0.16 μM respectively. These data indicate that PGHS-2 catalytically consumes NO during peroxidase turnover and that pro-inflammatory cytokines simultaneously upregulate NO synthesis and degradation pathways in murine macrophages. Catalytic NO consumption by PGHS-2 represents a novel interaction between NO and PGHS-2 that may impact on the biological effects of NO in vascular signalling and inflammation.

Nitric oxide and pro-inflammatory cytokines correlate with pain intensity in chronic pain patients

2007 ◽  
Vol 56 (1) ◽  
pp. 32-37 ◽  
Author(s):  
A. Koch ◽  
K. Zacharowski ◽  
O. Boehm ◽  
M. Stevens ◽  
P. Lipfert ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Chronic Pain ◽  
Pain Intensity ◽  
Inflammatory Cytokines ◽  
Chronic Pain Patients ◽  
Pain Patients ◽  
Pro Inflammatory Cytokines

scholarly journals Anti-Inflammatory Activity of Sonchus oleraceus Extract in Lipopoly saccharide-Stimulated RAW264.7 Cells

2018 ◽  
Vol 11 (4) ◽  
pp. 1755-1761
Author(s):  
Eun-Jin Yang ◽  
Sungchan Jang ◽  
Kwang Hee Hyun ◽  
Eun-Young Jung ◽  
Seung-Young Kim ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Cytokines ◽  
Inflammatory Activity ◽  
Raw264.7 Cells ◽  
Supporting Evidence ◽  
Dependent Manner ◽  
Sonchus Oleraceus ◽  
Raw264.7 Macrophages ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

The anti-inflammatory activity and non-toxicity of Sonchus oleraceus extract (J6) were tested by measuring its effect on the levels of nitric oxide (NO), prostaglandin E2 (PGE2), and the pro-inflammatory cytokines, interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. We treated the RAW264.7 cells with various concentrations (50, 100, or 200 μg/mL) of J6. Our results showed that J6 inhibited the production of NO, PGE2, and pro-inflammatory cytokines in a concentration-dependent manner, without compromising cell viability. In addition, we provided supporting evidence that the inhibitory activity of J6 on the production of NO and PGE2 occurred via the downregulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), respectively. Our findings suggest that J6 is a new source for anti-inflammatory drugs and ingredients for healthcare products that include functional cosmetics.

scholarly journals Ex Vivo Rumex Crispus and Cordyceps Sinensis Mixture Regulates Immune Cells Responses to Pro-inflammatory Cytokines inC57BL/6 mice Splenocytes

2018 ◽  
Author(s):  
Eui-Seong Park ◽  
Gyl-Hoon Song ◽  
Seung-Min Lee ◽  
Yong-Gyu Kim ◽  
Kun-Young Park
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Cytokines ◽  
Immune Cells ◽  
Cordyceps Sinensis ◽  
No Production ◽  
Mrna Levels ◽  
Rumex Crispus ◽  
Enhanced Production ◽  
Cox 2 ◽  
Pro Inflammatory Cytokines

We investigated the efficacy of a Rumex crispus and Cordyceps sinensis mixture made using the Beopje (Korea traditional processing method to remove anti-nutrients and enhance phytochemicals) method to regulate immune cell responses toward nitric oxide (NO) production, pro-inflammatory cytokines, and inflammation related genes in mice splenocytes. The six experimental groups were as follows: control (control), Rc-Cs (Rumex crispus (Rc) and Cordyceps sinensis (Cs) mixture, 6:4), TMC (Taemyeongcheong, commercial healthy drink containing Rc-Cs), LPS (lipopolysaccharide), LPS+Rc-Cs, and LPS+TMC. The Rc-Cs mixture reduced nitric oxide (NO) production in LPS-induced splenocytes. Moreover, Rc-Cs enhanced production of the pro-inflammatory cytokines TNF-α, IFN-γ, IL-1β, and IL-6 compared to the control (no treatment). However, Rc-Cs inhibited production of pro-inflammatory cytokines in LPS-induced splenocytes. In addition, LPS+Rc-Cs also significantly suppressed mRNA expression of IL-1β and IL-6 compared to LPS treatment. Interestingly, Rc-Cs did not increase mRNA levels of iNOS and COX-2, which are inflammation related genes compared to the control, while LPS+Rc-Cs reduced mRNA levels of iNOS and COX-2 compared LPS alone (p < 0.05). TMC showed a similar pattern compared to Rc-Cs. Therefore, Rc-Cs treatment in splenocytes enhanced NO production and pro-inflammatory cytokines compared to the control, whereas Rc-Cs treatment in LPS-induced splenocytes reduced NO production, pro-inflammatory cytokines, and inflammation related genes. Thus, Rc-Cs regulated immune cells responses by increasing pro-inflammatory cytokines in splenocytes and reducing toxin (LPS)-induced inflammation. These results indicate that a Rumex crispus and Cordyceps sinensis mixture (Rc-Cs) and TMC containing Rc-Cs promote immune cells responses and anti-inflammatory activities.

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