The transcription factor KLF14 regulates macrophage glycolysis and immune function by inhibiting HK2 in sepsis

AbstractSepsis is a heterogeneous syndrome induced by a dysregulated host response to infection. Glycolysis plays a role in maintaining the immune function of macrophages, which is crucial for severely septic patients. However, how the pathways that link glycolysis and macrophages are regulated is still largely unknown. Here, we provide evidence to support the function of KLF14, a novel Krüppel-like transcription factor, in the regulation of glycolysis and the immune function of macrophages during sepsis. KLF14 deletion led to significantly increased mortality in lethal models of murine endotoxemia and sepsis. Mechanistically, KLF14 decreased glycolysis and the secretion of inflammatory cytokines by macrophages by inhibiting the transcription of HK2. In addition, we confirmed that the expression of KLF14 was upregulated in septic patients. Furthermore, pharmacological activation of KLF14 conferred protection against sepsis in mice. These findings uncover a key role of KLF14 in modulating the inflammatory signaling pathway and shed light on the development of KLF14-targeted therapeutics for sepsis.

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The Role of the Transcription Factor CREB in Immune Function

The Journal of Immunology ◽

10.4049/jimmunol.1001829 ◽

2010 ◽

Vol 185 (11) ◽

pp. 6413-6419 ◽

Cited By ~ 359

Author(s):

Andy Y. Wen ◽

Kathleen M. Sakamoto ◽

Lloyd S. Miller

Keyword(s):

Transcription Factor ◽

Immune Function

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Chemical Activation of the Ethylene Signaling Pathway Promotes Fusarium graminearum Resistance in Detached Wheat Heads

Phytopathology ◽

10.1094/phyto-08-18-0286-r ◽

2019 ◽

Vol 109 (5) ◽

pp. 796-803 ◽

Cited By ~ 13

Author(s):

Nora A. Foroud ◽

Reyhaneh Pordel ◽

Ravinder K. Goyal ◽

Daria Ryabova ◽

Anas Eranthodi ◽

...

Keyword(s):

Signaling Pathway ◽

Fusarium Graminearum ◽

Host Response ◽

Chemical Activation ◽

Disease Spread ◽

Plant Signaling ◽

Head Blight ◽

Wheat Genotypes ◽

Ethylene Signaling Pathway

Plant signaling hormones such as ethylene have been shown to affect the host response to various pathogens. Often, the resistance responses to necrotrophic fungi are mediated through synergistic interactions of ethylene (ET) with the jasmonate signaling pathway. On the other hand, ET is also an inducer of senescence and cell death, which could be beneficial for some invading necrotrophic pathogens. Fusarium graminearum, a causative agent in Fusarium head blight of wheat, is a hemibiotrophic pathogen, meaning it has both biotrophic and necrotrophic phases during the course of infection. However, the role of ET signaling in the host response to Fusarium spp. is unclear; some studies indicate that ET mediates resistance, while others have shown that it is associated with susceptibility. These discrepancies could be related to various aspects of different experimental designs, and suggest that the role of ET signaling in the host response to FHB is potentially dependent on interactions with some undetermined factors. To investigate whether wheat genotype can influence the ET-mediated response to FHB, the effect of chemical treatments affecting the ET pathway was studied in six wheat genotypes in detached-head assays. ET-inhibitor treatments broke down resistance to both initial infection and disease spread in three resistant wheat genotypes, whereas ET-enhancer treatments resulted in reduced susceptibility in three susceptible genotypes. The results presented here show that the ET signaling can mediate FHB resistance to F. graminearum in different wheat backgrounds.

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The Possible Anti-Inflammatory Effect of Dehydrocostus Lactone on DSS-Induced Colitis in Mice

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/5659738 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8 ◽

Cited By ~ 2

Author(s):

Qing Zhou ◽

Wei-xin Zhang ◽

Zong-qi He ◽

Ben-sheng Wu ◽

Zhao-feng Shen ◽

...

Keyword(s):

Signaling Pathway ◽

Inflammatory Cytokines ◽

Activity Index ◽

Disease Activity Index ◽

Mucosal Barrier ◽

Protective Mechanism ◽

Inflammatory Signaling ◽

Anti Inflammatory ◽

Dehydrocostus Lactone ◽

Inflammatory Effect

Background. Dehydrocostus lactone (DL), one of the main active constituents in Aucklandia lappa Decne. (Muxiang), reported to have anti-inflammatory, antiulcer, and immunomodulatory properties. However, the effect of DL on ulcerative colitis (UC) has not been reported. To analyze the anti-inflammatory potential role of DL in UC, we provide a mechanism for the pharmacological action of DL. Methods. The experimental model of UC was induced by using oral administration of 2% dextran sulfate sodium (DSS) with drinking water in BALB/c mice. Mesalazine (Mes, 0.52 g/kg/d), DL-high doses (DL-H, 20 mg/kg/d), DL-middle doses (DL-M, 15 mg/kg/d), DL-low doses (DL-L, 10 mg/kg/d) were gavaged once a day from day 4 to day 17. Disease activity index (DAI) was calculated daily. On day 18, mice were rapidly dissected and the colorectal tissues were used to detect the levels of UC-related inflammatory cytokines (TNF-α, IL-1β, MCP-1, MPO, SOD, IL-6, IL-17, and IL-23), IL-6/STAT3 inflammatory signaling pathway (iNOS, COX2, IL-6, GP130, L-17, and IL-23), and colorectal mucosal barrier-related regulatory factors (MUC2, XBP1s, and α-defensins) by ELISA or qRT-PCR. Results. DL reduced the colorectal inflammation histological assessment, decreased UC-related inflammatory cytokines (TNF-α, IL-1β, MCP-1, MPO, SOD, IL-6, IL-17, and IL-23), downregulated IL-6/STAT3 inflammatory signaling pathway (iNOS, COX2, IL-6, GP130, L-17, and IL-23), repaired the key colorectal mucosal barrier protein-MUC2, and inhibited the downstream pathway (XBP1s and α-defensin). Conclusions. DL possessed the potential of anti-inflammatory effect to treated colitis. The protective mechanism of DL may involve in reducing inflammation and improving colorectal barrier function via downregulating the IL-6/STAT3 signaling.

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Pregnancy-Associated Plasma Protein A Induces Inflammatory Cytokine Expression by Activating IGF-I/PI3K/Akt Pathways

Mediators of Inflammation ◽

10.1155/2019/8436985 ◽

2019 ◽

Vol 2019 ◽

pp. 1-12 ◽

Cited By ~ 1

Author(s):

Weiping Li ◽

Hongwei Li ◽

Li Zhou ◽

Zijian Wang ◽

Bing Hua

Keyword(s):

Signaling Pathway ◽

Inflammatory Cytokines ◽

Plasma Protein ◽

Inflammatory Cytokine ◽

Protein A ◽

Dependent Manner ◽

Coronary Syndrome ◽

Raw264.7 Macrophages ◽

Igf I

Pregnancy-associated plasma protein A (PAPP-A) was previously reported to be an inflammatory biomarker and a prognostic marker of acute coronary syndrome (ACS) and involved in the process of atherosclerosis and plaque rupture. However, the role of PAPP-A in inflammation is poorly understood. In this study, we aimed to investigate the role of PAPP-A in macrophage activation and inflammatory cytokine production. RAW264.7 macrophages were treated with or without PAPP-A. Reverse-transcriptase quantitative real-time PCR (RT-qPCR) and Western blot were performed to detect gene and protein expressions. The concentration of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in culture supernatants was determined by ELISA. Results showed that PAPP-A significantly stimulated the expression of MCP-1, TNF-α, and IL-6 at both transcriptional and translational levels in a dose-dependent and time-dependent manner. The secretion of these inflammatory cytokines by macrophages was also increased after PAPP-A treatment. Moreover, PAPP-A activated the IGF-I/PI3K/Akt signaling pathway in macrophages. The PAPP-A-mediated upregulation of MCP-1, TNF-α, and IL-6 mRNA and protein levels were strongly inhibited by PI3K inhibitors or IGF-IR siRNA, indicating that the upregulation of MCP-1, TNF-α, and IL-6 could involve the IGF-I/PI3K/Akt pathway. Together, this study demonstrates that PAPP-A activates the macrophage signaling pathway (IGF-I/PI3K/Akt), which drives the expression and production of inflammatory cytokines known to contribute to the initiation and progression of ACS. These findings indicate that PAPP-A may play a proinflammatory role in the pathophysiology of ACS and serve as a potential therapeutic target.

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Hhex regulates the specification and growth of the hepatopancreatic ductal system

10.1101/330779 ◽

2018 ◽

Cited By ~ 1

Author(s):

Alethia Villasenor ◽

Sébastien Gauvrit ◽

Michelle M. Collins ◽

Silvia Parajes ◽

Hans-Martin Maischein ◽

...

Keyword(s):

Endothelial Cells ◽

Transcription Factor ◽

Bile Duct ◽

Common Bile Duct ◽

Blood Vessels ◽

Molecular Mechanisms ◽

Distinct Population ◽

System Formation ◽

Shed Light

SUMMARYSignificant efforts have advanced our understanding of foregut-derived organ development; however, little is known about the molecular mechanisms that underlie the formation of the hepatopancreatic ductal (HPD) system. Here, we report a role for the homeodomain transcription factor Hhex in directing HPD progenitor specification in zebrafish. Loss of Hhex function results in impaired HPD system formation. We found that Hhex specifies a distinct population of HPD progenitors that gives rise to the cystic duct, common bile duct, and extra-pancreatic duct. Since hhex is not uniquely expressed in the HPD region but is also expressed in endothelial cells and the yolk syncytial layer (YSL), we tested the role of blood vessels as well as the YSL in HPD formation. We found that blood vessels are required for HPD patterning, but not for HPD progenitor specification. In addition, we found that Hhex is required in both the endoderm and the YSL for HPD development. Our results shed light on the mechanisms necessary to direct endodermal progenitors towards the HPD fate and also advance our understanding of HPD system formation.

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Dietary choline enhanced skin immune response of juvenile grass carp might be related to STAT3 and NF-kB signaling pathway (Ctenopharyngodon idella)

10.21203/rs.3.rs-118695/v1 ◽

2020 ◽

Author(s):

Ze-Hong Yuan ◽

Lin Feng ◽

Wei-dan Jiang ◽

Pei Wu ◽

Yang Liu ◽

...

Keyword(s):

Immune Function ◽

Signaling Pathway ◽

Inflammatory Cytokines ◽

Grass Carp ◽

Protein Level ◽

Mrna Abundance ◽

Ctenopharyngodon Idella ◽

Fish Health ◽

Underlying Mechanisms ◽

Dietary Choline

Abstract Background: Choline is an indispensable vitamin of fish; which deficiency affects fish health. Fish health is affected by skin immune function. Hence, the present study was conducted to investigate the effects of dietary choline on skin immune function as well as underlying mechanisms of juvenile grass carp (Ctenopharyngodon idella).Results: The results exhibited that dietary choline (1) advanced the content of phosphatidylcholine (PC), betaine, and choline in grass crap skin (P < 0.05), up-regulated the mRNA abundance of choline transporter CHT1, CTL5, and CTL1 indicating that dietary choline could increase the contents of choline might be connected with choline transporters in the grass carp skin; (2) receded skin lesion and increased the level of IgM, C4, C3, and the activities of acid phosphatase (ACP) and lysozyme activity (LZ), raised mucin2, β-defensin, hepcidin, and LEAP-2B mRNA abundance (rather than LEAP-2A), down-regulated pro-inflammatory cytokines mRNA abundance (IFN-γ2, IL-15, TNF-α, IL-6, IL-12P40, and IL-1β) in skin of juvenile grass carp (P < 0.05), up-regulated anti-inflammatory cytokines mRNA abundance ( IL-10, IL-4/13A, TGF-β1, IL-11, and IL-4/13B) in grass crap skin (P < 0.05) demonstrating that choline enhanced the skin immune function; (3) down-regulated the mRNA abundance of IKKγ, NF-κBp52, , IKKβ, c-Rel, NF-κBp65, STAT3b2, STAT3b1 JAK1, and JAK2 as well as protein level of NF-κBp65 and p-STAT3 Tyr705 in nucleus, inhibited the mRNA and protein level of IkBα (P < 0.05), indicating that choline enhanced immune function might be relevant to JAK/STAT3 and NF-κB signaling pathway in fish skin.Conclusions: In conclusion, choline enhanced the skin immune function might be relate to JAK/STAT3 and NF-κB signaling molecules in fish. Furthermore, based on immune indices of grass carp (9.28-108.97g) skin (C3 and IgM contents as well as ACP activities), the choline requirements were estimated to be 1475.81, 1364.24, and 1574.37 mg/kg diet, respectively.

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Critical Role of STAT5 Transcription Factor Tetramerization for Cytokine Responses and Normal Immune Function

Immunity ◽

10.1016/j.immuni.2012.02.017 ◽

2012 ◽

Vol 36 (4) ◽

pp. 586-599 ◽

Cited By ~ 106

Author(s):

Jian-Xin Lin ◽

Peng Li ◽

Delong Liu ◽

Hyun Tak Jin ◽

Jianping He ◽

...

Keyword(s):

Transcription Factor ◽

Immune Function ◽

Critical Role ◽

Cytokine Responses ◽

Stat5 Transcription Factor ◽

Normal Immune Function

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miR-128 participates in the pathogenesis of chronic constipation by regulating the p38α/M-CSF inflammatory signaling pathway

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00114.2021 ◽

2021 ◽

Vol 321 (4) ◽

pp. G436-G447

Author(s):

Yuntian Hong ◽

Xianghai Ren ◽

Weicheng Liu ◽

Kongliang Sun ◽

Baoxiang Chen ◽

...

Keyword(s):

Signaling Pathway ◽

Murine Model ◽

Chronic Constipation ◽

Inflammatory Signaling ◽

Signaling Mechanism

In this study, we constructed a murine model and identified a novel signaling mechanism involved in the chronic constipation progression. Our findings on the role of miR-128/p38α/M-CSF axis provide new insights into the treatment of chronic constipation.

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Association between metabolic syndrome and periodontitis: The role of lipids, inflammatory cytokines, altered host response, and the microbiome

Periodontology 2000 ◽

10.1111/prd.12379 ◽

2021 ◽

Vol 87 (1) ◽

pp. 50-75

Author(s):

Flavia Q. Pirih ◽

Sepehr Monajemzadeh ◽

Neelima Singh ◽

Rachel Sheridan Sinacola ◽

Jae Min Shin ◽

...

Keyword(s):

Metabolic Syndrome ◽

Inflammatory Cytokines ◽

Host Response

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AKR1B10 accelerates the production of pro-inflammatory cytokines via NF-κB signaling pathway in colon cancer

10.21203/rs.2.17573/v1 ◽

2019 ◽

Author(s):

Cong Liu ◽

Lei Shi ◽

Wanyun Li ◽

Zilan Huang ◽

Shengyu Wang ◽

...

Keyword(s):

Colon Cancer ◽

Signaling Pathway ◽

Inflammatory Cytokines ◽

Molecular Mechanisms ◽

Reductase Activity ◽

Clinical Stage ◽

Clinicopathological Characteristics ◽

The Relationship ◽

Pro Inflammatory Cytokines

Abstract Aldo-keto reductase family 1, member B10 (AKR1B10) has been reported to be involved in tumorigenesis of various cancer. In our studies, we evaluated the relationship between AKR1B10 expression and clinicopathological characteristics in colon cancer and showed that AKR1B10 expression was significantly correlated with TNM stage and clinical stage of colon cancer. It has been reported that colorectal cancer is closely associated with chronic inflammation and the underlying molecular mechanisms are still elusive. Here we found that knockdown of AKR1B10 significantly decreased the expression of the inflammatory cytokines, IL1α and IL6, induced by lipopolysaccharide (LPS) via inhibiting NF-κB signaling pathway. Furthermore, AKR1B10 depends on its reductase activity to affect the NF-κB signaling pathway and subsequently affect the production of inflammatory cytokines. In addition, knockdown of AKR1B10 effectively reduced cell proliferation and clonogenic growth, indicating the biologic role of AKR1B10 in colon cancer. Collectively, our findings provided important insights into a previously unrecognized role of AKR1B10 in colon cancer.

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