Inhibitory effects of alternaramide on inflammatory mediator expression through TLR4-MyD88-mediated inhibition of NF-кB and MAPK pathway signaling in lipopolysaccharide-stimulated RAW264.7 and BV2 cells

Surfactant protein A (SP-A), the most abundant pulmonary surfactant protein, plays a role in innate host defense and blocks the inhibitory effects of serum proteins on surfactant surface tension-lowering properties. SP-A mRNA and protein are downregulated by phorbol esters (TPA) via inhibition of gene transcription. We evaluated the TPA signaling pathways involved in SP-A inhibition in a lung cell line, H441 cells. TPA caused sustained phosphorylation of p44/42 mitogen-activated protein kinase (MAPK), p38 MAPK, and c-Jun-NH2-terminal kinase. An inhibitor of conventional and novel isoforms of protein kinase C (PKC) and two inhibitors of p44/42 MAPK kinase partially or completely blocked the inhibitory effects of TPA on SP-A mRNA levels. In contrast, inhibitors of conventional PKC-α and -β, stress-activated protein kinases, protein phosphatases, protein kinase A, and the phosphatidylinositol 3-kinase pathway had no effect on the TPA-mediated inhibition of SP-A mRNA. TPA also stimulated the synthesis of c-Jun mRNA and protein in a time-dependent manner. Inhibitors of the p44/42 MAPK signaling pathway and PKC blocked the TPA-mediated phosphorylation of p44/42 MAPK and the increase in c-Jun mRNA. We conclude that TPA inhibits SP-A gene expression via novel isoforms of PKC, the p44/42 MAPK pathway, and the activator protein-1 complex.

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Inhibitory Effects of Ginkgo biloba Extract on Inflammatory Mediator Production by Porphyromonas gingivalis Lipopolysaccharide in Murine Macrophages via Nrf-2 Mediated Heme Oxygenase-1 Signaling Pathways

Inflammation ◽

10.1007/s10753-012-9461-6 ◽

2012 ◽

Vol 35 (4) ◽

pp. 1477-1486 ◽

Cited By ~ 12

Author(s):

Eun Yeon Ryu ◽

Ah Jeong Park ◽

Sun Young Park ◽

Sung Hae Park ◽

Hye Won Eom ◽

...

Keyword(s):

Signaling Pathways ◽

Porphyromonas Gingivalis ◽

Heme Oxygenase ◽

Ginkgo Biloba ◽

Inflammatory Mediator ◽

Ginkgo Biloba Extract ◽

Heme Oxygenase 1 ◽

Inhibitory Effects ◽

Inflammatory Mediator Production ◽

Porphyromonas Gingivalis Lipopolysaccharide

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Crosstalk between lncRNA DANCR and miR-125b-5p in HCC cell progression

Tumori Journal ◽

10.1177/0300891620977010 ◽

2020 ◽

pp. 030089162097701

Author(s):

Ling Yang ◽

Mi-Na Jiang ◽

Yang Liu ◽

Chao-Qun Wu ◽

Hong Liu

Keyword(s):

Noncoding Rna ◽

Caspase 3 ◽

Mapk Pathway ◽

Negative Control ◽

Luciferase Reporter ◽

Inhibitory Effects ◽

Expression Levels ◽

Cell Progression ◽

Polymerase Chain ◽

Hcc Cells

Objective: To investigate the mechanism of long noncoding RNA (lncRNA) DANCR on the progression of hepatocellular carcinoma (HCC) cells. Methods: The expression levels of DANCR and miR-125b-5p were measured in normal hepatocytes (LO2) and HCC cell lines by quantitative reverse transcription polymerase chain reaction. HepG2 and Huh-7 cells were transfected with sh-DANCR, the negative control (sh-NC), miR-125b-5p mimic, or mimic NC or cotransfected with sh-DANCR and miR-125b-5p inhibitor. HCC cell proliferation was assessed through CCK8 and plate colony formation assay. Western blot quantified the expression levels of Bcl-2, Bax, caspase-3, and cleaved-caspase-3. Apoptotic rate was detected as well as migratory and invasive capacities. The implication of the MAPK signal pathway was assessed by detecting the expression levels of p38, ERK1/2, JNK, p-p38, p-ERK1/2, and p-JNK. Interactions between DANCR and miR-125b-5p were detected by dual luciferase reporter assay. Results: In HCC cells, DANCR was highly expressed and miR-125b-5p was decreased. sh-DANCR or miR-125b-5p mimic stimulation reduced HepG2 or Huh-7 cell progression while promoted cell apoptosis evidenced by increased apoptotic rate, elevated levels of Bax and cleaved-caspase-3, and decreased Bcl-2. Moreover, the migration rate and invasiveness of HCC cells were also inhibited by sh-DANCR and miR-125b-5p mimic. Levels of p-p38/p38, p-ERK1/2/ERK1/2, and p-JNK/JNK were suppressed by sh-DANCR and miR-125b-5p mimic. LncRNA DANCR negatively targeted and directly bound to miR-125b-5p. Knockdown of miR-125b-5p could reverse the inhibitory effects of sh-DANCR on HCC cells. Conclusion: In HCC cells, lncRNA DANCR sponges miR-125b-5p and activates MAPK pathway, thus facilitating HCC cell progression.

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The p38 MAPK pathway inhibits tristetraprolin-directed decay of interleukin-10 and pro-inflammatory mediator mRNAs in murine macrophages

FEBS Letters ◽

10.1016/j.febslet.2009.04.039 ◽

2009 ◽

Vol 583 (12) ◽

pp. 1933-1938 ◽

Cited By ~ 72

Author(s):

Corina Tudor ◽

Francesco P. Marchese ◽

Edward Hitti ◽

Anna Aubareda ◽

Lesley Rawlinson ◽

...

Keyword(s):

P38 Mapk ◽

Inflammatory Mediator ◽

Mapk Pathway ◽

Interleukin 10 ◽

Murine Macrophages ◽

P38 Mapk Pathway

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Additive and Inhibitory Effects of Simultaneous Treatment with Growth Factors on DNA Synthesis through MAPK Pathway and G1 Cyclins in Rat Hepatocytes

Biochemical and Biophysical Research Communications ◽

10.1006/bbrc.2000.4063 ◽

2001 ◽

Vol 280 (1) ◽

pp. 368-373 ◽

Cited By ~ 30

Author(s):

Akihiro Moriuchi ◽

Shuichi Hirono ◽

Akio Ido ◽

Toshimasa Ochiai ◽

Tetsufumi Nakama ◽

...

Keyword(s):

Growth Factors ◽

Dna Synthesis ◽

Mapk Pathway ◽

Rat Hepatocytes ◽

Inhibitory Effects ◽

Simultaneous Treatment ◽

G1 Cyclins

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Paclitaxel Inhibits Synoviocyte Migration and Inflammatory Mediator Production in Rheumatoid Arthritis

Frontiers in Pharmacology ◽

10.3389/fphar.2021.714566 ◽

2021 ◽

Vol 12 ◽

Author(s):

Xiaochen Chen ◽

Haofeng Lin ◽

Jinyang Chen ◽

Lisheng Wu ◽

Junqing Zhu ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Inflammatory Mediator ◽

Mapk Pathway ◽

Bone Destruction ◽

New Drugs ◽

Mitogen Activated Protein Kinase ◽

Dependent Manner ◽

Inflammatory Mediator Production ◽

Tnf Α ◽

Mitogen Activated Protein

Activated fibroblast-like synoviocytes (FLSs) play a crucial role in the pathogenesis and progression of rheumatoid arthritis (RA). It is urgent to develop new drugs that can effectively inhibit the abnormal activation of RA-FLS. In our study, the RA-FLS cell line, MH7A, and mice with collagen-induced arthritis (CIA) were used to evaluate the effect of paclitaxel (PTX). Based on the results, PTX inhibited the migration of RA-FLS in a dose-dependent manner and significantly reduced the spontaneous expression of IL-6, IL-8, and RANKL mRNA and TNF-α-induced transcription of the IL-1β, IL-8, MMP-8, and MMP-9 genes. However, PTX had no significant effect on apoptosis in RA-FLS. Mechanistic studies revealed that PTX significantly inhibited the TNF-α-induced phosphorylation of ERK1/2 and JNK in the mitogen-activated protein kinase (MAPK) pathway and suppressed the TNF-α-induced activation of AKT, p70S6K, 4EBP1, and HIF-1α in the AKT/mTOR pathway. Moreover, PTX alleviated synovitis and bone destruction in CIA mice. In conclusion, PTX inhibits the migration and inflammatory mediator production of RA-FLS by targeting the MAPK and AKT/mTOR signaling pathways, which provides an experimental basis for the potential application in the treatment of RA.

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Biology and therapeutic potential of interleukin-10

Journal of Experimental Medicine ◽

10.1084/jem.20190418 ◽

2019 ◽

Vol 217 (1) ◽

Cited By ~ 16

Author(s):

Margarida Saraiva ◽

Paulo Vieira ◽

Anne O’Garra

Keyword(s):

T Cell Activation ◽

Cell Activation ◽

Inflammatory Mediator ◽

Therapeutic Potential ◽

Cd8 T Cell ◽

Interleukin 10 ◽

Clinical Settings ◽

Inhibitory Effects ◽

Epithelial Repair ◽

Adipose Cells

The cytokine IL-10 is a key anti-inflammatory mediator ensuring protection of a host from over-exuberant responses to pathogens and microbiota, while playing important roles in other settings as sterile wound healing, autoimmunity, cancer, and homeostasis. Here we discuss our current understanding of the regulation of IL-10 production and of the molecular pathways associated with IL-10 responses. In addition to IL-10’s classic inhibitory effects on myeloid cells, we also describe the nonclassic roles attributed to this pleiotropic cytokine, including how IL-10 regulates basic processes of neural and adipose cells and how it promotes CD8 T cell activation, as well as epithelial repair. We further discuss its therapeutic potential in the context of different diseases and the outstanding questions that may help develop an effective application of IL-10 in diverse clinical settings.

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