scholarly journals Rac1 signaling regulates LPS-induced mouse mastitis via inhibition of NLRP3, NF-κB and MAPK signaling pathways

2020 ◽  
Author(s):  
Chaoqun Wang ◽  
Aimin Jiang ◽  
Wang Jingjing ◽  
Xiao Liu ◽  
Han Zhen ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Signaling Pathways ◽  
Inflammatory Responses ◽  
Bovine Mastitis ◽  
Specific Inhibitor ◽  
Nuclear Factor Κb ◽  
Mapk Signaling ◽  
New Drugs ◽  
Mitogen Activated Protein Kinase ◽  
Pcr Analysis

Abstract Background Bovine mastitis characterized by mammary gland inflammatory responses, is the most frequent and costly diseases in dairy cattle. Researchers have been seeking effective treatments for this disease, but still not very successful. Ras-related C3 botulinum toxin substrate 1 (Rac1) is implicated in various cellular functions, including apoptosis, ROS production and inflammatory responses, and presents an attractive therapeutic target for many diseases. However, the effects of Rac1 signaling on mastitis remain unclear. The aim of this study is to investigate the effects of Rac1 signaling on mastitis via inhibition by Rac1 specific inhibitor NSC23766 based on a murine model of lipoplysaccharide (LPS)-induced mastitis. Methods Murine mastitis model was established by perfusion of LPS, hematoxylin-eosin (H & E) staining was employed to explore the mechanisms in mouse model, qRT- PCR analysis, Western blotting analysis. Results The results revealed that NSC23766 significantly decreased the damage of mammary gland by LPS, reduced myeloperoxidase activities, and the productions of IL-1β, IL-6, TNF-α and MCP-1 gene expression in the mammary glands with LPS perfusion. Moreover, western blot analysis showed that NSC23766 inhibited the phosphoryation of p65, IκBα, ERK, and p38, and suppressed the expression of NLRP3. Conclusion These findings suggested that administration of NSC23766 prevented the development of mastitis by inhibiting NLRP3, mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways. Accordingly, this study may provide research basis for the development of new drugs against mastitis, and NSC23766 might be a potential therapeutic drugs for mastitis.

Panax notoginseng Saponins Modulate the Inflammatory Response and Improve IBD-Like Symptoms via TLR/NF-κB and MAPK Signaling Pathways

2021 ◽  
pp. 1-15
Author(s):  
Hua Luo ◽  
Chi Teng Vong ◽  
Dechao Tan ◽  
Jinming Zhang ◽  
Hua Yu ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Signaling Pathways ◽  
Inflammatory Responses ◽  
Panax Notoginseng ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Clinical Effects ◽  
Protective Effects ◽  
Panax Notoginseng Saponins

Panax notoginseng saponins (PNS) are the main active ingredients of Panax notoginseng (Burk) F. H. Chen, which are used as traditional Chinese medicine for thousands of years and have various clinical effects, including anti-inflammation, anti-oxidation, and cardiovascular protection. Inflammatory bowel disease (IBD) is a complex gastrointestinal inflammatory disease that cannot be cured completely nowadays. The anti-inflammatory and protective effects of PNS were analyzed in vitro and in dextran sulfate sodium (DSS)-induced colitis mouse model. PNS inhibited the release of nitric oxide (NO), tumor necrosis factor-[Formula: see text] (TNF-[Formula: see text], interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) in Pam3CSK4-induced RAW 264.7 macrophages. In the animal study, compared with DSS-induced mice, PNS reduced the expression of pro-inflammatory cytokines (TNF-[Formula: see text], IL-6, and MCP-1) in the colon tissues. Furthermore, PNS treatment led to a remarkable reduction in the activation of the inhibitor of nuclear factor kappa-B kinase [Formula: see text]/[Formula: see text] (IKK[Formula: see text]/[Formula: see text], I[Formula: see text]B[Formula: see text] and p65 induced by DSS. On the other hand, PNS inhibited the phosphorylation of c-Jun N-terminal kinase (JNK), p38, and extracellular regulated protein kinase 1/2 (ERK1/2). Taken together, our results suggested that PNS conferred profound protection for colitis mice through the downregulation of mitogen-activated protein kinase (MAPK) and NF-[Formula: see text]B signaling pathways, which were associated with reducing inflammatory responses, alleviating tissue damage, and maintaining of intestinal integrity and functionality.

scholarly journals Expression, Subcellular Localization, and Interactions of CPK Family Genes in Maize

2019 ◽  
Vol 20 (24) ◽  
pp. 6173
Author(s):  
Muhammad Hayder Bin Khalid ◽  
Muhammad Ali Raza ◽  
Hao Qiang Yu ◽  
Imran Khan ◽  
Fu Ai Sun ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Calcium Signaling ◽  
Signaling Pathways ◽  
Defense Mechanism ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Pcr Analysis ◽  
Phylogenetic Groups ◽  
Positive Interaction ◽  
Cdna Sequences

Calcium-dependent protein kinase (CPKs) is a key player in the calcium signaling pathway to decode calcium signals into various physiological responses. cDNA sequences of 9 ZmCPK genes were successfully cloned from all four phylogenetic groups in maize. qRT-PCR analysis showed the expression variation of these selected genes under abscisic acid (ABA) and calcium chloride (CaCl2) treatment. Due to the presence of N-myristoylation/palmitoylation sites, the selected ZmCPK members were localized in a plasma membrane. To clarify whether ZmCPK, a key player in calcium signaling, interacts with key players of ABA, protein phosphatase 2Cs (PP2Cs) and the SNF1-related protein kinase 2s (SnRK2s) and mitogen-activated protein kinase (MAPK) signaling pathways in maize, we examined the interaction between 9 CPKs, 8 PP2Cs, 5 SnRKs, and 20 members of the MPK family in maize by using yeast two-hybrid assay. Our results showed that three ZmCPKs interact with three different members of ZmSnRKs while four ZmCPK members had a positive interaction with 13 members of ZmMPKs in different combinations. These four ZmCPK proteins are from three different groups in maize. These findings of physical interactions between ZmCPKs, ZmSnRKs, and ZmMPKs suggested that these signaling pathways do not only have indirect influence but also have direct crosstalk that may involve the defense mechanism in maize. The present study may improve the understanding of signal transduction in plants.

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 Artemisinin Protects Porcine Mammary Epithelial Cells against Lipopolysaccharide-Induced Inflammatory Injury by Regulating the NF-κB and MAPK Signaling Pathways

Animals ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1528
Author(s):  
Wenfei Zhang ◽  
Liang Xiong ◽  
Jiaming Chen ◽  
Zhezhe Tian ◽  
Jiaxin Liu ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Signaling Pathways ◽  
Mammary Epithelial Cells ◽  
Nuclear Factor Κb ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Inflammatory Factors ◽  
Tnf Α ◽  
Expression Abundance ◽  
Anti Inflammatory

Artemisinin performs a variety of biological functions, such as anti-cancer, anti-inflammatory, anti-viral, and anti-oxidant effects. However, the effects of artemisinin on sow mastitis have not been studied. The results of the current study showed that mRNA expression abundance and content of the inflammatory factors interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), and interleukin-6 (IL-6) were significantly increased when using 50 μg/mL LPS to stimulate pMECs for 24 h (p < 0.05). Pretreatment with 20 μM artemisinin weakened LPS-induced inflammatory damage in pMECs and decreased mRNA expression abundance and the content of inflammatory factors (IL-1β, IL-6, and TNF-α) in pMECs (p < 0.05). Mechanistically, artemisinin inhibited LPS-induced activation of the mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways. In summary, the pretreatment of pMECs with artemisinin showed enhanced anti-inflammatory activity against LPS-induced inflammation.

scholarly journals Effects of Deoxynivalenol and Mycotoxin Adsorbent Agents on Mitogen-Activated Protein Kinase Signaling Pathways and Inflammation-Associated Gene Expression in Porcine Intestinal Epithelial Cells

Toxins ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 301
Author(s):  
Yu-Hsiang Yu ◽  
Yi-Han Lai ◽  
Felix Shih-Hsiang Hsiao ◽  
Yeong-Hsiang Cheng
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Signaling Pathways ◽  
Inflammatory Responses ◽  
Intestinal Epithelial Cells ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Intestinal Epithelial ◽  
Mycotoxin Adsorbent ◽  
Mapk Signaling Pathways

Deoxynivalenol (DON) is the most prevalent mycotoxin in swine feedstuffs. The intestinal epithelial cells represent the first target for the DON. Here, we studied the effects of DON and mycotoxin adsorbent agents on mitogen-activated protein kinase (MAPK) signaling pathways and inflammation-associated gene expression in porcine intestinal epithelial cells (IPEC-J2). Results showed that phosphorylation of MAPK signaling pathways (p38, ERK, and JNK) was increased after treatment of DON or lipopolysaccharide (LPS) in IPEC-J2 cells. The phosphorylation of p38, ERK, and JNK was not further enhanced after co-treatment with DON and LPS. The inos and cox-2 mRNA expression were significantly induced at 6 h after treatment of DON. DON treatment significantly increased the claudin 3 and occludin mRNA expression at 12 h. DON in combination with LPS treatment did not further increase the inflammation and tight junction-associated gene expression. The DON-induced phosphorylation of MAPK signaling pathways was impaired by mycotoxin adsorbent agent (nanoscale silicate platelets and the mixture of montmorillonites and yeast cell walls) treatment, thereby decreasing inflammation and tight junction-associated gene expression. Taken together, these findings demonstrate that DON triggers the inflammation in IPEC-J2 cells by phosphorylation of MAPK signaling pathways and LPS does not further augment the DON-induced inflammatory responses. Mycotoxin adsorbent agents can attenuate DON-induced inflammatory responses in IPEC-J2 cells through modulation of the phosphorylation of p38, ERK, and JNK.

scholarly journals Transcriptomic Profiling Reveals a Role for TREM-1 Activation in Enterovirus D68 Infection-Induced Proinflammatory Responses

2021 ◽  
Vol 12 ◽  
Author(s):  
Jinyu Li ◽  
Shan Yang ◽  
Sihua Liu ◽  
Yulu Chen ◽  
Hongyun Liu ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Transcriptional Profiling ◽  
Specific Inhibitor ◽  
Respiratory Illness ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Health Concern ◽  
Necrosis Factor Alpha ◽  
Acute Flaccid Myelitis ◽  
Enterovirus D68

Increasing cases related to the pathogenicity of Enterovirus D68 (EV-D68) have made it a growing worldwide public health concern, especially due to increased severe respiratory illness and acute flaccid myelitis (AFM) in children. There are currently no vaccines or medicines to prevent or treat EV-D68 infections. Herein, we performed genome-wide transcriptional profiling of EV-D68-infected human rhabdomyosarcoma (RD) cells to investigate host-pathogen interplay. RNA sequencing and subsequent experiments revealed that EV-D68 infection induced a profound transcriptional dysregulation of host genes, causing significantly elevated inflammatory responses and altered antiviral immune responses. In particular, triggering receptor expressed on myeloid cells 1 (TREM-1) is involved in highly activated TREM-1 signaling processes, acting as an important mediator in EV-D68 infection, and it is related to upregulation of interleukin 8 (IL-8), IL-6, IL-12p70, IL-1β, and tumor necrosis factor alpha (TNF-α). Further results demonstrated that NF-κB p65 was essential for EV-D68-induced TREM-1 upregulation. Moreover, inhibition of the TREM1 signaling pathway by the specific inhibitor LP17 dampened activation of the p38 mitogen-activated protein kinase (MAPK) signaling cascade, suggesting that TREM-1 mainly transmits activation signals to phosphorylate p38 MAPK. Interestingly, treatment with LP17 to inhibit TREM-1 inhibited viral replication and infection. These findings imply the pathogenic mechanisms of EV-D68 and provide critical insight into therapeutic intervention in enterovirus diseases.

scholarly journals Phosphothreonine Lyase Promotes p65 Degradation in a Mitogen-Activated Protein Kinase/Mitogen- and Stress-Activated Protein Kinase 1-Dependent Manner

2018 ◽  
Vol 87 (1) ◽  
Author(s):  
Mingyu Hou ◽  
Wenhui Wang ◽  
Feizi Hu ◽  
Yuanxing Zhang ◽  
Dahai Yang ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Pathogenic Bacteria ◽  
Critical Role ◽  
Nuclear Factor Κb ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Dependent Manner ◽  
Content Type ◽  
Catalytic Active Site ◽  
Mitogen Activated Protein

ABSTRACT Bacterial phosphothreonine lyases have been identified to be type III secretion system (T3SS) effectors that irreversibly dephosphorylate host mitogen-activated protein kinase (MAPK) signaling to promote infection. However, the effects of phosphothreonine lyase on nuclear factor κB (NF-κB) signaling remain largely unknown. In this study, we detected significant phosphothreonine lyase-dependent p65 degradation during Edwardsiella piscicida infection in macrophages, and this degradative effect was blocked by the protease inhibitor MG132. Further analysis revealed that phosphothreonine lyase promotes the dephosphorylation and ubiquitination of p65 by inhibiting the phosphorylation of mitogen- and stress-activated protein kinase-1 (MSK1) and by inhibiting the phosphorylation of extracellular signal-related kinase 1/2 (ERK1/2), p38α, and c-Jun N-terminal kinase (JNK). Moreover, we revealed that the catalytic active site of phosphothreonine lyase plays a critical role in regulating the MAPK-MSK1-p65 signaling axis. Collectively, the mechanism described here expands our understanding of the pathogenic effector in not only regulating MAPK signaling but also regulating p65. These findings uncover a new mechanism by which pathogenic bacteria overcome host innate immunity to promote pathogenesis.

scholarly journals MAP Kinase OsMEK2 and OsMPK1 Signaling for Ferroptotic Cell Death in Rice-Magnaporthe oryzae Interactions

2020 ◽  
Author(s):  
Sarmina Dangol ◽  
Raksha Singh ◽  
Khoa Nam Nguyen ◽  
Yafei Chen ◽  
Juan Wang ◽  
...  
Keyword(s):  
Cell Death ◽  
Map Kinase ◽  
Signaling Pathways ◽  
Magnaporthe Oryzae ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Microbial Pathogens ◽  
Blast Disease ◽  
Related Cell ◽  
Mitogen Activated Protein

ABSTRACTMitogen-activated protein kinase (MAPK) signaling is required for plant cell death responses to invading microbial pathogens. Ferric ions and reactive oxygen species (ROS) accumulate in rice (Oryza sativa) tissues undergoing cell death during Magnaporthe oryzae infection. Here, we report that rice MAP kinase (OsMEK2 and OsMPK1) signaling cascades are involved in iron- and ROS-dependent ferroptotic cell death responses of rice to M. oryzae infection. OsMEK2 interacted with OsMPK1 in the cytoplasm, and OsMPK1 moved from the cytoplasm into the nucleus to bind to the OsWRKY90 transcription factor. OsMEK2 expression may trigger OsMPK1-OsWRKY90 signaling pathways in the nucleus. Avirulent M. oryzae infection in ΔOsmek2 mutant rice did not trigger iron and ROS accumulation and lipid peroxidation, and also downregulated OsMPK1, OsWRKY90, OsRbohB, and OsPR-1b expression. However, OsMEK2 overexpression induced ROS-and iron-dependent cell death in rice during M. oryzae infection. The downstream MAP kinase (OsMPK1) overexpression induced ROS- and iron-dependent ferroptotic cell death in the compatible rice-M. oryzae interaction. These data suggest that the OsMEK2-OsMPK1-OsWRKY90 signaling cascade is involved in the ferroptotic cell death in rice. The small-molecule inducer erastin triggered iron- and lipid ROS-dependent, but OsMEK2-independent, ferroptotic cell death in ΔOsmek2 mutant plants during M. oryzae infection. Disease-related cell death was lipid ROS-dependent and iron-independent in the ΔOsmek2 mutant plants. These combined results suggest that OsMEK2 and OsMPK1 expression positively regulates iron- and ROS-dependent ferroptotic cell death via OsMEK2-OsMPK1-OsWRKY90 signaling pathways, and blast disease (susceptibility)-related cell death was ROS-dependent but iron-independent in rice-M. oryzae interactions.

scholarly journals The effects of 50 Hz magnetic field–exposed cell culture medium on cellular functions in FL cells

2019 ◽  
Vol 60 (4) ◽  
pp. 424-431 ◽  
Author(s):  
Yue Fei ◽  
Liling Su ◽  
Haifeng Lou ◽  
Chuning Zhao ◽  
Yiqin Wang ◽  
...  
Keyword(s):  
Cell Viability ◽  
Signaling Pathways ◽  
Relative Permittivity ◽  
Culture Medium ◽  
Biological Effects ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Cell Counting ◽  
International Agency ◽  
Dependent Manner

Abstract Although extremely low frequency magnetic fields (ELF-MFs) have been classified as a possible carcinogen for humans by the International Agency for Research on Cancer (IARC), their biological effects and underlying mechanisms are still unclear. Our previous study indicated that ELF-MF exposure influenced the relative permittivity of the saline solution, suggesting that the MF exposure altered physical properties of the solution. To explore the biophysical mechanism of ELF-MF–induced biological effects, this study examined the effects of 50 Hz sinusoidal MF at 0–4.0 mT on the permittivity of culture medium with phase-interrogation surface plasmon resonance (SPR) sensing. Then, the biological effects of MF pre-exposed culture medium on cell viability, the mitogen-activated protein kinase (MAPK) signaling pathways, oxidative stress, and genetic stabilities were analyzed using Cell Counting Kit-8, western blot, flow cytometry, γH2AX foci formation, and comet assay. The results showed that SPR signals were decreased under MF exposure in a time- and dose-dependent manner, and the decreased SPR signals were reversible when the exposure was drawn off. However, MF pre-exposed culture medium did not significantly change cell viability, intracellular reactive oxygen species level, activation of the MARK signaling pathways, or genetic stabilities in human amniotic epithelial cells (FL cells). In conclusion, our data suggest that the relative permittivity of culture medium was influenced by 50 Hz MF exposure, but this change did not affect the biological processes in FL cells.

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