scholarly journals Physalin B Suppresses Inflammatory Response to Lipopolysaccharide in RAW264.7 Cells by Inhibiting NF-κB Signaling

2018 ◽  
Vol 2018 ◽  
pp. 1-6
Author(s):  
Yanjun Yang ◽  
Lang Yi ◽  
Qing Wang ◽  
Bingbing Xie ◽  
Congwei Sha ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Inflammatory Response ◽  
Tumor Necrosis ◽  
Nuclear Translocation ◽  
Biological Activities ◽  
Raw264.7 Macrophages ◽  
Naturally Occurring ◽  
Physalis Angulata ◽  
Anti Inflammatory ◽  
Necrosis Factor

Physalin B from Physalis angulata L. (Solanaceae) is a naturally occurring secosteroid with multiple biological activities. But its anti-inflammatory activity and mechanism remain unclear. Physalin B effects on RAW264.7 macrophages stimulated by lipopolysaccharide (LPS) were observed in this study. The expression and secretion of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) induced by LPS were significantly inhibited by physalin B. Meanwhile, the NF-κB nuclear translocation induced by LPS was inhibited by physalin B. The anti-inflammatory effects of physalin B could not be inhibited by mifepristone (RU486), the blocker of glucocorticoid receptor. In conclusion, physalin B can suppress inflammatory response to LPS in macrophages by inhibiting the production of inflammatory cytokines via NF-κB signaling.

scholarly journals Beneficial Dysregulation of the Time Course of Inflammatory Mediators in Lipopolysaccharide-Induced Tumor Necrosis Factor Alpha Factor-Deficient Mice

2010 ◽  
Vol 17 (5) ◽  
pp. 699-704 ◽  
Author(s):  
Sreedevi Srinivasan ◽  
Susan E. Leeman ◽  
Salomon Amar
Keyword(s):  
Tumor Necrosis Factor ◽  
Inflammatory Response ◽  
Inflammatory Cytokines ◽  
Tumor Necrosis ◽  
Time Course ◽  
Lethal Dose ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Anti Inflammatory ◽  
Necrosis Factor

ABSTRACT To begin to understand the surprising survival of macrophage-specific lipopolysaccharide-induced tumor necrosis factor alpha factor-deficient (macLITAF−/−) animals after a lethal dose of lipopolysaccharide (LPS), as reported earlier, the present follow-up study focuses on the role of LITAF in the regulation of inflammatory cytokines secreted in response to lethal or sublethal doses of LPS administered to wild-type (WT) and macLITAF−/− mice. A time course study of kinase expression in peritoneal macrophages revealed increased phosphorylation of prosurvival kinases Akt, Erk1/2, and ribosomal S6 kinase (RSK) in macLITAF−/− mice compared to that in WT mice (n = 8), confirming their role in LPS-mediated diseases. macLITAF−/− mice (n = 8) survived a lethal dose of LPS plus d-galactosamine (d-GalN), expressing lower serum levels of pro- and anti-inflammatory cytokines than the WT levels. To extend our knowledge on LPS-induced inflammatory events, an effective sublethal dose of LPS was administered to the animals (n = 14). WT animals exhibited an acute inflammatory response that decreased after 4 h. Interestingly, macLITAF−/− mice exhibited an initial delay in the secretion of proinflammatory cytokines that peaked after 8 h and reached WT levels after 18 h. Anti-inflammatory cytokine secretions were initially delayed but increased after 4 h and remained elevated compared to WT levels, even after 18 h. Our results demonstrate that LITAF deficiency in vivo affects cytokines other than TNF-α and influences the balance between the pro- and anti-inflammatory cytokines, which protects the animals from the deleterious effects of an LPS-induced inflammatory response, resulting in a beneficial host regulation of inflammatory cytokines and in enhanced survival. Therapeutic intervention aimed at reducing LITAF via kinase modulators may prove useful in preventing LPS-induced mortality.

scholarly journals Indole-Terpenoids With Anti-inflammatory Activities From Penicillium sp. HFF16 Associated With the Rhizosphere Soil of Cynanchum bungei Decne

2021 ◽  
Vol 12 ◽  
Author(s):  
Guojun Pan ◽  
Yanfen Zhao ◽  
Shuang Ren ◽  
Fengyang Liu ◽  
Qicai Xu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Tumor Necrosis Factor ◽  
Spectroscopic Data ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Rhizosphere Soil ◽  
Raw264.7 Macrophages ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Necrosis Factor

Four new indole-terpenoids (1–4) named encindolene A, 18-O-methyl-encindolene A, encindolene B, and encindolene C, as well as three known analogs (5–7), were isolated from the fungus Penicillium sp. HFF16 from the rhizosphere soil of Cynanchum bungei Decne. The structures of compounds including absolute configurations were elucidated by spectroscopic data and electronic circular dichroism (ECD) analysis. Anti-inflammatory activity evaluation revealed that compounds 1–7 inhibit the production of nitric oxide with IC50 values of 79.4, 49.7, 81.3, 40.2, 86.7, 90.1, and 54.4 μM, respectively, and decrease the levels of tumor necrosis factor-α, interleukin-6 contents in lipopolysaccharide-induced RAW264.7 macrophages.

scholarly journals A Novel Curcumin-Mycophenolic Acid Conjugate Inhibited Hyperproliferation of Tumor Necrosis Factor-Alpha-Induced Human Keratinocyte Cells

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 956
Author(s):  
Yonelian Yuyun ◽  
Pahweenvaj Ratnatilaka Na Bhuket ◽  
Wiwat Supasena ◽  
Piyapan Suwattananuruk ◽  
Kemika Praengam ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Mycophenolic Acid ◽  
Tumor Necrosis ◽  
Molecular Mechanisms ◽  
Cellular Transport ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Anti Inflammatory ◽  
Necrosis Factor

Curcumin (CUR) has been used as adjuvant therapy for therapeutic application in the treatment of psoriasis through several mechanisms of action. Due to the poor oral bioavailability of CUR, several approaches have been developed to overcome the limitations of CUR, including the prodrug strategy. In this study, CUR was esterified with mycophenolic acid (MPA) as a novel conjugate prodrug. The MPA-CUR conjugate was structurally elucidated using FT-IR, 1H-NMR, 13C-NMR, and MS techniques. Bioavailable fractions (BFs) across Caco-2 cells of CUR, MPA, and MPA-CUR were collected for further biological activity evaluation representing an in vitro cellular transport model for oral administration. The antipsoriatic effect of the BFs was determined using antiproliferation and anti-inflammation assays against hyperproliferation of tumor necrosis factor-alpha (TNF-α)-induced human keratinocytes (HaCaT). The BF of MPA-CUR provided better antiproliferation than that of CUR (p < 0.001). The enhanced hyperproliferation suppression of the BF of MPA-CUR resulted from the reduction of several inflammatory cytokines, including IL-6, IL-8, and IL-1β. The molecular mechanisms of anti-inflammatory activity were mediated by an attenuated signaling cascade of MAPKs protein, i.e., p38, ERK, and JNK. Our results present evidence for the MPA-CUR conjugate as a promising therapeutic agent for treating psoriasis by antiproliferative and anti-inflammatory actions.

scholarly journals The α and β Subunits of IκB Kinase (IKK) Mediate TRAF2-Dependent IKK Recruitment to Tumor Necrosis Factor (TNF) Receptor 1 in Response to TNF

2001 ◽  
Vol 21 (12) ◽  
pp. 3986-3994 ◽  
Author(s):  
Anne Devin ◽  
Yong Lin ◽  
Shoji Yamaoka ◽  
Zhiwei Li ◽  
Michael Karin ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Leucine Zipper ◽  
Nuclear Translocation ◽  
Ring Finger ◽  
Tnf Receptor ◽  
Death Domain ◽  
Iκb Kinase ◽  
Cytokine Tumor Necrosis Factor ◽  
Necrosis Factor

ABSTRACT The activation of IκB kinase (IKK) is a key step in the nuclear translocation of the transcription factor NF-κB. IKK is a complex composed of three subunits: IKKα, IKKβ, and IKKγ (also called NEMO). In response to the proinflammatory cytokine tumor necrosis factor (TNF), IKK is activated after being recruited to the TNF receptor 1 (TNF-R1) complex via TNF receptor-associated factor 2 (TRAF2). We found that the IKKα and IKKβ catalytic subunits are required for IKK-TRAF2 interaction. This interaction occurs through the leucine zipper motif common to IKKα, IKKβ, and the RING finger domain of TRAF2, and either IKKα or IKKβ alone is sufficient for the recruitment of IKK to TNF-R1. Importantly, IKKγ is not essential for TNF-induced IKK recruitment to TNF-R1, as this occurs efficiently in IKKγ-deficient cells. Using TRAF2−/− cells, we demonstrated that the TNF-induced interaction between IKKγ and the death domain kinase RIP is TRAF2 dependent and that one possible function of this interaction is to stabilize the IKK complex when it interacts with TRAF2.

scholarly journals Herpes Simplex Virus 1 E3 Ubiquitin Ligase ICP0 Protein Inhibits Tumor Necrosis Factor Alpha-Induced NF-κB Activation by Interacting with p65/RelA and p50/NF-κB1

2013 ◽  
Vol 87 (23) ◽  
pp. 12935-12948 ◽  
Author(s):  
Jie Zhang ◽  
Kezhen Wang ◽  
Shuai Wang ◽  
Chunfu Zheng
Keyword(s):  
Tumor Necrosis Factor ◽  
Ubiquitin Ligase ◽  
Tumor Necrosis ◽  
Nuclear Translocation ◽  
E3 Ubiquitin Ligase ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor ◽  
Hsv 1

NF-κB plays central roles in regulation of diverse biological processes, including innate and adaptive immunity and inflammation. HSV-1 is the archetypal member of the alphaherpesviruses, with a large genome encoding over 80 viral proteins, many of which are involved in virus-host interactions and show immune modulatory capabilities. In this study, we demonstrated that the HSV-1 ICP0 protein, a viral E3 ubiquitin ligase, was shown to significantly suppress tumor necrosis factor alpha (TNF-α)-mediated NF-κB activation. ICP0 was demonstrated to bind to the NF-κB subunits p65 and p50 by coimmunoprecipitation analysis. ICP0 bound to the Rel homology domain (RHD) of p65. Fluorescence microscopy demonstrated that ICP0 abolished nuclear translocation of p65 upon TNF-α stimulation. Also, ICP0 degraded p50 via its E3 ubiquitin ligase activity. The RING finger (RF) domain mutant ICP0 (ICP0-RF) lost its ability to inhibit TNF-α-mediated NF-κB activation and p65 nuclear translocation and degrade p50. Notably, the RF domain of ICP0 was sufficient to interact with p50 and abolish NF-κB reporter gene activity. Here, it is for the first time shown that HSV-1 ICP0 interacts with p65 and p50, degrades p50 through the ubiquitin-proteasome pathway, and prevents NF-κB-dependent gene expression, which may contribute to immune evasion and pathogenesis of HSV-1.

scholarly journals Palmitic Acid Induces Production of Proinflammatory Cytokines Interleukin-6, Interleukin-1β, and Tumor Necrosis Factor-αvia a NF-κB-Dependent Mechanism in HaCaT Keratinocytes

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Bing-rong Zhou ◽  
Jia-an Zhang ◽  
Qian Zhang ◽  
Felicia Permatasari ◽  
Yang Xu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Necrosis Factor ◽  
Palmitic Acid ◽  
Interleukin 6 ◽  
Tumor Necrosis ◽  
Nuclear Translocation ◽  
Pyrrolidine Dithiocarbamate ◽  
Hacat Keratinocytes ◽  
Stat3 Phosphorylation ◽  
Necrosis Factor

To investigate whether palmitic acid can be responsible for the induction of inflammatory processes, HaCaT keratinocytes were treated with palmitic acid at pathophysiologically relevant concentrations. Secretion levels of interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), NF-κB nuclear translocation, NF-κB activation, Stat3 phosphorylation, and peroxisome proliferator-activated receptor alpha (PPARα) mRNA and protein levels, as well as the cell proliferation ability were measured at the end of the treatment and after 24 hours of recovery. Pyrrolidine dithiocarbamate (PDTC, a selective chemical inhibitor of NF-κB) and goat anti-human IL-6 polyclonal neutralizing antibody were used to inhibit NF-κB activation and IL-6 production, respectively. Our results showed that palmitic acid induced an upregulation of IL-6, TNF-α, IL-1βsecretions, accompanied by NF-κB nuclear translocation and activation. Moreover, the effect of palmitic acid was accompanied by PPARαactivation and Stat3 phosphorylation. Palmitic acid-induced IL-6, TNF-α, IL-1βproductions were attenuated by NF-κB inhibitor PDTC. Palmitic acid was administered in amounts able to elicit significant hyperproliferation and can be attenuated by IL-6 blockage. These data demonstrate for the first time that palmitic acid can stimulate IL-6, TNF-α, IL-1βproductions in HaCaT keratinocytes and cell proliferation, thereby potentially contributing to acne inflammation and pilosebaceous duct hyperkeratinization.

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