scholarly journals Genetic and Epigenetic Impact of Chronic Inflammation on Colon Mucosa Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Jia He ◽  
Jimin Han ◽  
Jia Liu ◽  
Ronghua Yang ◽  
Jingru Wang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Chronic Inflammation ◽  
Inflammatory Responses ◽  
Mutation Accumulation ◽  
Genetic Mutation ◽  
Mapk Signaling ◽  
Cancer Development ◽  
Differentially Methylated Region ◽  
Colon Mucosa ◽  
Indel Mutation

Chronic inflammation increases cancer risk, and cancer development is characterized by stepwise accumulation of genetic and epigenetic alterations. During chronic inflammation, infectious agents and intrinsic mediators of inflammatory responses can induce genetic and epigenetic changes. This study tried to evaluate both the genetic and epigenetic influence of chronic inflammation on colon mucosa cells. Repetitive dextran sulfate sodium (DSS) treatment induced chronic colitis model. Whole-exome sequencing (WES) (200× coverage) was performed to detect somatic variations in colon mucosa cells. With the use of whole-genome bisulfite sequencing (BS) at 34-fold coverage (17-fold per strand), the methylome of both the colitis and control tissue was comparatively analyzed. Bioinformatics assay showed that there was no significant single-nucleotide polymorphism/insertion or deletion (SNP/InDel) mutation accumulation in colitis tissue, while it accumulated in aged mice. Forty-eight genes with SNP/InDel mutation were overlapped in the three colitis tissues, two (Wnt3a and Lama2) of which are in the cancer development-related signaling pathway. Differentially methylated region (DMR) assay showed that many genes in the colitis tissue are enriched in the cancer development-related signaling pathway, such as PI3K–AKT, Ras, Wnt, TGF-beta, and MAPK signaling pathway. Together, these data suggested that even though chronic inflammation did not obviously increase genetic mutation accumulation, it could both genetically and epigenetically alter some genes related to cancer development.

scholarly journals Analyses of long non-coding RNA and mRNA profiling in the spleen of diarrheic piglets caused by Clostridium perfringens type C

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5997 ◽  
Author(s):  
Zunqiang Yan ◽  
Xiaoyu Huang ◽  
Wenyang Sun ◽  
Qiaoli Yang ◽  
Hairen Shi ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Clostridium Perfringens ◽  
Diarrheal Disease ◽  
Inflammatory Responses ◽  
Expression Profiles ◽  
Mapk Signaling ◽  
Non Coding Rna ◽  
Receptor Signaling Pathway ◽  
Type C ◽  
Long Non Coding Rna

Background Clostridium perfringens (C. perfringens) type C is the most common bacteria causing piglet diarrheal disease and it greatly affects the economy of the global pig industry. The spleen is an important immune organ in mammals; it plays an irreplaceable role in resisting and eradicating pathogenic microorganisms. Based on different immune capacity in piglets, individuals display the resistance and susceptibility to diarrhea caused by C. perfringens type C. Recently, long non-coding RNA (lncRNA) and mRNA have been found to be involved in host immune and inflammatory responses to pathogenic infections. However, little is known about spleen transcriptome information in piglet diarrhea caused by C. perfringens type C. Methods Hence, we infected 7-day-old piglets with C. perfringens type C to lead to diarrhea. Then, we investigated lncRNA and mRNA expression profiles in spleens of piglets, including control (SC), susceptible (SS), and resistant (SR) groups. Results As a result, 2,056 novel lncRNAs and 2,417 differentially expressed genes were found. These lncRNAs shared the same characteristics of fewer exons and shorter length. Bioinformatics analysis identified that two lncRNAs (ALDBSSCT0000006918 and ALDBSSCT0000007366) may be involved in five immune/inflammation-related pathways (such as Toll-like receptor signaling pathway, MAPK signaling pathway, and Jak-STAT signaling pathway), which were associated with resistance and susceptibility to C. perfringens type C infection. This study contributes to the understanding of potential mechanisms involved in the immune response of piglets infected with C. perfringens type C.

Fermented ginseng attenuates lipopolysaccharide-induced inflammatory responses by activating the TLR4/MAPK signaling pathway and remediating gut barrier

2021 ◽  
Author(s):  
Jingjing Fan ◽  
Sitong Liu ◽  
Zhiyi Ai ◽  
Yiying Chen ◽  
Yonghong Wang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Inflammatory Responses ◽  
Mapk Signaling ◽  
Physiological Effect ◽  
Mapk Signaling Pathway ◽  
Gut Barrier ◽  
Fermented Ginseng ◽  
Anti Inflammatory

Generally, ginsenosides have the physiological effect of an anti-inflammatory immunity.

scholarly journals MACROD1/LRP16 Enhances LPS-Stimulated Inflammatory Responses by Up-Regulating a Rac1-Dependent Pathway in Adipocytes

2018 ◽  
Vol 51 (6) ◽  
pp. 2591-2603 ◽  
Author(s):  
Li Zang ◽  
Quan Hong ◽  
Guoqing Yang ◽  
Weijun Gu ◽  
Anping Wang ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Signaling Pathway ◽  
Target Genes ◽  
Inflammatory Responses ◽  
Specific Inhibitor ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Human Adipocytes ◽  
Rac1 Expression

Background/Aims: Chronic inflammation contributes to the development of type 2 diabetes mellitus by targeting the insulin receptor substrate protein-1 (IRS-1) signaling pathway. Previous studies showed that Leukemia related protein 16 (LRP16) reduced insulin stimulated glucose uptake in adipocytes by impairing the IRS-1 signaling pathway. We explored the mechanism by which LRP16 promotes the inflammatory response. Methods: We screened LRP16 induced proteins in the lipopolysaccharide (LPS)-stimulated inflammatory response using liquid chromatography-mass spectrometry (LC-MS) and analyzed the potential biological functions of these proteins using online bioinformatics tools. mRNA expression and protein expression of target genes were measured by real time PCR and Western blot, respectively. Results: A total of 390 differentially expressed proteins were identified. The mitogen-activated protein kinase (MAPK) signaling pathway was the primary activated pathway in LRP16-expressing cells. Overexpression of LRP16 activated ERK1/2 and Rac1, which are two key players related to the MAPK signaling pathway. Furthermore, knock down of endogenous LRP16 by RNA interference (RNAi) reduced Rac1 expression, ERK activation, and inflammatory cytokine expression in human adipocytes stimulated by LPS. The stimulatory effect of LRP16 was diminished by suppressing Rac1 expression and treating the cells with the ERK specific inhibitor, PD98059. Conclusion: These findings revealed the functions of LRP16 in promoting the inflammatory response through activating the Rac1-MAPK1/ERK pathway in human adipocytes.

scholarly journals Coral-Derived Endophytic Fungal Product, Butyrolactone-I, Alleviates Lps Induced Intestinal Epithelial Cell Inflammatory Response Through TLR4/NF-κB and MAPK Signaling Pathways: An in vitro and in vivo Studies

2021 ◽  
Vol 8 ◽  
Author(s):  
Shengwei Chen ◽  
Yi Zhang ◽  
Xueting Niu ◽  
Sahar Ghulam Mohyuddin ◽  
Jiayin Wen ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Tight Junction ◽  
Signaling Pathway ◽  
Inflammatory Responses ◽  
Intestinal Barrier ◽  
Mapk Signaling ◽  
In Vivo Studies ◽  
Protective Effects ◽  
Tnf Α ◽  
Junction Protein

Herein, we assessed the anti-inflammatory and intestinal barrier protective effects of butyrolactone-I (BTL-1), derived from the coral-derived endophytic fungus (Aspergillus terreus), using the LPS-induced IPEC-J2 inflammation model and the DSS-induced IBD model in mice. In IPEC-J2 cells, pretreatment with BTL-I significantly inhibited TLR4/NF-κB signaling pathway and JNK phosphorylation, resulting in the decrease of IL-1β and IL-6 expression. Interestingly, BTL-1 pretreatment activated the phosphorylation of ERK and P38, which significantly enhanced the expression of TNF-α. Meanwhile, BTL-1 pretreatment upregulated tight junction protein expression (ZO-1, occludin, and claudin-1) and maintained intestinal barrier and intestinal permeability integrity. In mice, BTL-1 significantly alleviated the intestinal inflammatory response induced by DSS, inhibited TLR4/NF-κB signaling pathway, and MAPK signaling pathway, thus reducing the production of IL-1, IL-6, and TNF-α. Further, the expression of tight junction proteins (ZO-1, occludin, and claudin-1) was upregulated in BTL-1 administrated mice. Therefore, it has been suggested that butyrolactone-I alleviates inflammatory responses in LPS-stimulated IPEC-J2 and DSS-induced murine colitis by TLR4/NF-κB and MAPK signal pathway. Thereby, BTL-1 might potentially be used as an ocean drug to prevent intestinal bowel disease.

Exploring the Potential Mechanism of Shufeng Jiedu Capsule for Treating COVID-19 by Comprehensive Network Pharmacological Approaches and Molecular Docking Validation

2020 ◽  
Vol 23 ◽  
Author(s):  
Zhenjie Zhuang ◽  
Xiaoying Zhong ◽  
Huanhuan Zhang ◽  
Huiqi Chen ◽  
Boxiang Huang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Target Genes ◽  
Inflammatory Responses ◽  
Mapk Signaling ◽  
Binding Activity ◽  
Network Pharmacology ◽  
Therapeutic Effects ◽  
Holistic View ◽  
Chinese Patent ◽  
Molecule Docking

Objective: Shufeng Jiedu capsule (SFJDC) is a well-known Chinese patent drug that is recommended as a basic prescription and applied widely in the clinical treatment of COVID-19. However, the exact molecular mechanism of SFJDC remains unclear. The present study aims to determine the potential pharmacological mechanisms of SFJDC in the treatment of COVID-19 based on network pharmacology. Methods: The network pharmacology-based strategy includes collection and analysis of active compounds and target genes, network construction, identification of key compounds and hub target genes, KEGG and GO enrichment, recognition and analysis of main modules, as well as molecule docking. Results: A total of 214 active chemical compounds and 339 target genes of SFJDC were collected. Of note, 5 key compounds ( β -sitosterol, luteolin, kaempferol, quercetin, and stigmasterol) and 10 hub target genes (TP53, AKT1, NCOA1, EGFR, PRKCA, ANXA1, CTNNB1, NCOA2, RELA and FOS) were identified based on network analysis. The hub target genes mainly enriched in pathways including MAPK signaling pathway, PI3K-Akt signaling pathway and cAMP signaling pathway, which could be the underlying pharmacological mechanisms of SFJDC for treating COVID-19. Moreover, the key compounds had high binding activity with three typical target genes. Conclusions: y network pharmacology analysis, SFJDC was found to effectively improve immune function and reduce inflammatory responses based on its key compounds, hub target genes, and the relevant pathways. These findings may provide valuable evidence for explaining how SFJDC exerting the therapeutic effects on COVID-19, providing a holistic view for further clinical application.

Curcumenol isolated from Curcuma zedoaria suppresses Akt-mediated NF-κB activation and p38 MAPK signaling pathway in LPS-stimulated BV-2 microglial cells

2015 ◽  
Vol 6 (11) ◽  
pp. 3550-3559 ◽  
Author(s):  
Jia Ye Lo ◽  
Muhamad Noor Alfarizal Kamarudin ◽  
Omer Abdalla Ahmed Hamdi ◽  
Khalijah Awang ◽  
Habsah Abdul Kadir
Keyword(s):  
Signaling Pathway ◽  
P38 Mapk ◽  
Inflammatory Responses ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Microglial Cells ◽  
Curcuma Zedoaria

Curcumenol attenuates the inflammatory responses induced by LPS in BV-2 microglial cells.

scholarly journals Oleanolic Acid Acetate Exerts Anti-Inflammatory Activity via IKKα/β Suppression in TLR3-Mediated NF-κB Activation

Molecules ◽  
2019 ◽  
Vol 24 (21) ◽  
pp. 4002 ◽  
Author(s):  
Hyung Jin Lim ◽  
Hyun-Jae Jang ◽  
Mi Hwa Kim ◽  
Soyoung Lee ◽  
Seung Woong Lee ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Oleanolic Acid ◽  
Inflammatory Cytokines ◽  
Inflammatory Responses ◽  
Critical Role ◽  
Mapk Signaling ◽  
Dependent Manner ◽  
Nuclear Factor ◽  
Anti Inflammatory ◽  
Tlr3 Signaling

Oleanolic acid acetate (OAA), a major triterpenoid compound of Vigna angularis (azuki bean, V. angularis), has been shown to downregulate inflammatory responses in macrophages. Here, we show the molecular basis for the effect of OAA on Toll-like receptor (TLR) downstream signaling. OAA treatment significantly inhibited the secretion of embryonic alkaline phosphatase (SEAP) induced by polyinosinic acid (poly(I), TLR3 ligand) in a dose-dependent manner and without cytotoxicity in THP1-XBlue cells. In addition, OAA downregulated the gene expression of poly(I) induced pro-inflammatory cytokines and chemokines genes such as MCP-1, IL-1β, IL-8, VCAM-1 and ICAM-1. Furthermore, we found that the inhibition activity of OAA was accompanied by decreased activation of not only nuclear factor-kappa B (NF-κB) signaling but also mitogen-activated protein kinase (MAPK) signaling upon stimulation with the TLR3 agonist. Interestingly, the interaction of OAA with IκB kinase α/β (IKKα/β) strongly attenuated the production of certain proteins and inflammatory cytokines in the TLR3 signaling pathway, such as nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IkBα), extracellular regulated kinases (ERK), and p38, in an in vitro model. The action of OAA was regulated by TLR3, demonstrating that TLR3 plays a critical role in mediating the physiologically-relevant anti-inflammatory action of OAA and that the interaction with IKKα/β is modulated through TLR3. These results reveal new insight into the understanding of the regulatory mechanisms of the downstream TLR3 signaling pathway and consequent inflammatory responses that are involved in the development and progression of inflammatory diseases.

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