scholarly journals Wnt5a Regulates Odontoblast Inflammation by Promoting CCL2 Expression

2021 ◽  
Author(s):  
Ronghua Zhang ◽  
Wei Ge ◽  
Ruixue Huang ◽  
Zhao Meng ◽  
Xiaojie Xu ◽  
...  
Keyword(s):  
Western Blotting ◽  
Mapk Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Macrophage Migration ◽  
Chemokine Expression ◽  
Mapk Activity ◽  
Wnt5a Expression ◽  
Ccl2 Expression ◽  
Tnf Α ◽  
Raw264.7 Macrophage

Abstract Objective Wnt5a is involved inflammation, including pulpitis, by upregulating cytokine/chemokine expression. Odontoblasts are the first layer cells in dental pulp and respond to inflammatory stimuli. However, whether Wnt5a is involved in odontoblast inflammation is unclear. This study aimed to investigate the role of Wnt5a in odontoblast inflammation. Methods We measured and compared Wnt5a- or TNF-α-induced cytokine/chemokine expression in mouse odontoblast-like (17IIA11) cells by real-time PCR and Western blotting. Transwell assays were used to examine the effect of Wnt5a on RAW264.7 macrophage migration. We examined whether the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways were involved in the molecular mechanism of TNF-α or Wnt5a in 17IIA11 cells by Western blotting. Results TNF-α upregulated Wnt5a in odontoblasts. Wnt5a upregulated CCL2 expression in odontoblasts and enhanced RAW264.7 cell migration. We also found that TNF-α-induced Wnt5a expression was abrogated by inhibiting the MAPK pathway or NF-κB activity and that inhibiting MAPK activity could lead to decreased NF-κB activity. Conclusions Wnt5a is involved in the TNF-α-induced inflammatory response in odontoblasts. TNF-α upregulates Wnt5a expression via MAPK-dependent NF-κB activation in odontoblasts. Wnt5a upregulates CCL2 expression in odontoblasts and enhances RAW264.7 macrophage migration.

scholarly journals Camel Milk Attenuates Rheumatoid Arthritis Via Inhibition of Mitogen Activated Protein Kinase Pathway

2017 ◽  
Vol 43 (2) ◽  
pp. 540-552 ◽  
Author(s):  
Hany H. Arab ◽  
Samir A. Salama ◽  
Tamer M. Abdelghany ◽  
Hany A. Omar ◽  
El-Shaimaa A. Arafa ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Mapk Pathway ◽  
Lipid Peroxide ◽  
Mitogen Activated Protein Kinase ◽  
Camel Milk ◽  
Tnf Α ◽  
Mitogen Activated Protein ◽  
Anti Oxidant ◽  
Cox 2 ◽  
Anti Inflammatory

Background/Aims: Camel milk (CM) has shown beneficial anti-inflammatory actions in several experimental and clinical settings. So far, its effect on rheumatoid arthritis (RA) has not been previously explored. Thus, the current work aimed to evaluate the effects of CM in Adjuvant-induced arthritis and air pouch edema models in rats, which mimic human RA. Methods: CM was administered at 10 ml/kg orally for 3 weeks starting on the day of Freund’s adjuvant paw inoculation. The levels of TNF-α and IL-10 were measured by ELISA while the protein expression of NF-κBp65, COX-2 and iNOS was detected by immunohistochemistry. The expression of MAPK target proteins was assessed by Western blotting. Results: CM attenuated paw edema, arthritic index and gait score along with dorsal pouch inflammatory cell migration. CM lowered the TNF-α and augmented the anti-inflammatory IL-10 levels in sera and exudates of arthritic rats. It also attenuated the expression of activated NF-κBp65, COX-2 and iNOS in the lining of the dorsal pouch. Notably, CM inhibited the MAPK pathway signal transduction via lowering the phosphorylation of p38 MAPK, ERK1/2 and JNK1/2 in rat hind paws. Additionally, CM administration lowered the lipid peroxide and nitric oxide levels and boosted glutathione and total anti-oxidant capacity in sera and exudates of animals. Conclusion: The observed CM downregulation of the arthritic process may support the interest of CM consumption as an adjunct approach for the management of RA.

Neisseria meningitidis-mediates proinflammatory responses in PMN: Crosstalk TLR-2/c-JunN-Terminal

2018 ◽  
Vol 6 (4) ◽  
pp. 362-378
Author(s):  
Yanyan Xu ◽  
Hanan Slimani
Keyword(s):  
Neisseria Meningitidis ◽  
Mapk Pathway ◽  
Nuclear Factor Κb ◽  
Primary Response ◽  
Mitogen Activated Protein Kinase ◽  
Murine Bone Marrow ◽  
Tnf Α ◽  
Mitogen Activated Protein ◽  
Proinflammatory Responses ◽  
Meningitis In Children

Neisseria meningitidis is a Gram-negative bacterium emerging the leading cause of bacterial meningitis in children and young adult wide world. The host innate immune response against meningitis is largely unknown. In this study, we show that N.meningitidis robustly activates mRNA and protein expression of tumor necrosis factor (TNF-α) and interleukin (IL-6) in murine bone marrow-derived PMN. Toll-like receptor (TLR-2) and myeloid differentiation primary response gene 88 (MyD88), N.meningitidis also activates the mitogen-activated protein kinase (MAPKs; c-Jun N-terminal kinase (JNK), ERK1/2 and p38 MAPK) pathway. N.meningitidis-induced TNF-α and IL-6 production was dependent on JNK activation. The intracellular reactive oxygen species (ROS), NADPH oxidase-2, and nuclear factor-κB are required for N.meningitides-induced proinflammatory cytokine generation in PMN. Together, we have demonstrated that N.meningitidis-induced activation of host proinflammatory cytokines is mediated through TLR2-dependent JNK signaling pathways.

scholarly journals Paclitaxel Inhibits Synoviocyte Migration and Inflammatory Mediator Production in Rheumatoid Arthritis

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.

scholarly journals Differential Regulation of the Mitogen-Activated Protein Kinases by Pathogenic and Nonpathogenic Mycobacteria

2002 ◽  
Vol 70 (6) ◽  
pp. 3040-3052 ◽  
Author(s):  
Shannon K. Roach ◽  
Jeffrey S. Schorey
Keyword(s):  
Nitric Oxide ◽  
Effector Proteins ◽  
Mitogen Activated Protein Kinase ◽  
Necrosis Factor Alpha ◽  
Macrophage Response ◽  
Immune Effector ◽  
Murine Bone Marrow ◽  
Mapk Activity ◽  
Tnf Α ◽  
Mitogen Activated Protein

ABSTRACT Mycobacteria are the etiologic agents of numerous diseases which account for significant morbidity and mortality in humans and other animal species. Many mycobacteria are intramacrophage pathogens and therefore the macrophage response to infection, which includes synthesis of cytokines such as tumor necrosis factor alpha (TNF-α) and production of nitric oxide, has important consequences for host immunity. However, very little is known about the macrophage cell signaling pathways initiated upon infection or how pathogenic mycobacteria may modulate the macrophage responses. Using primary murine bone marrow macrophages, we established that p38 and extracellular signal-regulated kinases 1 and 2 of the mitogen-activated protein kinase (MAPK) pathways are activated upon infection with different species of mycobacteria. However, we observed decreased MAPK activity over time in macrophages infected with pathogenic Mycobacterium avium strains relative to infections with nonpathogenic mycobacteria. Furthermore, macrophages infected with M. avium produced lower levels of TNF-α, interleukin 1β, and inducible nitric oxide synthase 2 than macrophages infected with nonpathogenic species. Inhibitor studies indicate that the MAPKs are required for the Mycobacterium-mediated induction of these effector proteins. Our data indicate that MAPKs are activated in macrophages upon invasion by mycobacteria and that this activation is diminished in macrophages infected with pathogenic strains of M. avium, resulting in decreased production of important immune effector proteins. The decreased MAPK activation associated with M. avium infections suggests a novel point of immune intervention by this mycobacterial species.

Role of p38 mitogen-activated protein kinase in cardiac myocyte secretion of the inflammatory cytokine TNF-α

2001 ◽  
Vol 280 (5) ◽  
pp. H1970-H1981 ◽  
Author(s):  
Cherry Ballard-Croft ◽  
D. Jean White ◽  
David L. Maass ◽  
Dixie Peters Hybki ◽  
Jureta W. Horton
Keyword(s):  
Protein Kinase ◽  
P38 Mapk ◽  
Cardiac Myocyte ◽  
Total Body Surface Area ◽  
Mitogen Activated Protein Kinase ◽  
Kinase Assay ◽  
Burn Trauma ◽  
Mapk Activity ◽  
Tnf Α ◽  
Mitogen Activated Protein

This study examined the hypothesis that burn trauma promotes cardiac myocyte secretion of inflammatory cytokines such as tumor necrosis factor (TNF)-α and produces cardiac contractile dysfunction via the p38 mitogen-activated protein kinase (MAPK) pathway. Sprague-Dawley rats were divided into four groups: 1) sham burn rats given anesthesia alone, 2) sham burn rats given the p38 MAPK inhibitor SB203580 (6 mg/kg po, 15 min; 6- and 22-h postburn), 3) rats given third-degree burns over 40% total body surface area and treated with vehicle (1 ml of saline) plus lactated Ringer solution for resuscitation (4 ml · kg−1 · percent burn−1), and 4) burn rats given injury and fluid resuscitation plus SB203580. Rats from each group were killed at several times postburn to examine p38 MAPK activity (by Western blot analysis or in vitro kinase assay); myocardial function and myocyte secretion of TNF-α were examined at 24-h postburn. These studies showed significant activation of p38 MAPK at 1-, 2-, and 4-h postburn compared with time-matched shams. Burn trauma impaired cardiac mechanical performance and promoted myocyte secretion of TNF-α. SB203580 inhibited p38 MAPK activity, reduced myocyte secretion of TNF-α, and prevented burn-mediated cardiac deficits. These data suggest p38 MAPK activation is one aspect of the signaling cascade that culminates in postburn secretion of TNF-α and contributes to postburn cardiac dysfunction.

scholarly journals The mitogen-activated protein kinase pathway tonically inhibits both basal and IGF-I-stimulated IGF-binding protein-5 production in mammary epithelial cells

2007 ◽  
Vol 194 (2) ◽  
pp. 349-359 ◽  
Author(s):  
Jodie M Fleming ◽  
Jeffrey A Brandimarto ◽  
Wendie S Cohick
Keyword(s):  
Mammary Epithelial Cells ◽  
Mapk Pathway ◽  
Mammary Epithelial ◽  
Mitogen Activated Protein Kinase ◽  
Mapk Activity ◽  
Igf I ◽  
Mitogen Activated Protein ◽  
Igf Binding ◽  
Mapk Inhibitors ◽  
Igfbp 3

The IGF system plays a key role in mammary gland growth and development. Our lab previously reported that IGF-I primarily regulates IGF-binding protein (BP)-3 in bovine mammary epithelial cells (MEC) and IGFBP-5 in mammary fibroblasts (MF). Presently, we examined the signaling pathways used by IGF-I to elicit this distinct, cell-type specific regulation. The phosphatidylinositol-3 kinase pathway was required for IGF-I to increase IGFBP-3 and -5 in MF and IGFBP-3 in MEC. Surprisingly, inhibiting the mitogen-activated protein kinase (MAPK) pathway in MEC increased IGFBP-5 mRNA levels 2- to 4-fold under basal conditions and 8- to 12-fold in cells treated with IGF-I within 4 h. Similar patterns of IGFBP-3 and -5 regulation were observed in murine MEC. Cells treated with IGF-I in the presence of MAPK inhibitors secreted more IGFBP-5 protein into conditioned media relative to cells treated with IGF-I alone; however, IGFBP-5 protein was not detected in conditioned media of cells treated with only a MAPK inhibitor. The IGFBP-5 mRNA response to MAPK inhibitors was specific for MEC, as blocking MAPK activity decreased the ability of IGF-I to induce IGFBP-5 in MF. In addition, no other IGFBP was increased in either cell type when MAPK activity was inhibited. These increases in IGFBP-5 expression in response to inhibition of the MAPK pathway corresponded with the induction of apoptosis. In conclusion, we report the novel observation that the MAPK/extracellular signal regulated kinase (ERK) pathway specifically represses IGFBP-5 expression in MEC. The corresponding changes in apoptosis and IGFBP-5 expression support a role for this specific IGFBP in mammary gland involution.

Anti-Inflammatory Effects of Trilinolein from Panax notoginseng Through the Suppression of NF-κB and MAPK Expression and Proinflammatory Cytokine Expression

2014 ◽  
Vol 42 (06) ◽  
pp. 1485-1506 ◽  
Author(s):  
Shyh-Shyun Huang ◽  
Jeng-Shyan Deng ◽  
Jaung-Geng Lin ◽  
Chao-Ying Lee ◽  
Guan-Jhong Huang
Keyword(s):  
Nitric Oxide ◽  
Western Blotting ◽  
Mapk Pathway ◽  
Interleukin 1 ◽  
Nuclear Factor Κb ◽  
Paw Edema ◽  
Raw264.7 Macrophages ◽  
Tnf Α ◽  
Cox 2 ◽  
Anti Inflammatory

In this study, we have investigated the anti-inflammatory effects of trilinolein (TL) using a lipopolysaccharide (LPS)-stimulated mouse macrophage (RAW264.7) and carrageenan (Carr)-induced mouse paw edema model. When RAW264.7 macrophages were treated with different concentrations of TL together with LPS, a significant concentration-dependent inhibition of nitric oxide (NO), tumor necrosis factor (TNF-α), interleukin-1 (IL-1β), and IL-6 production was detected. Western blotting revealed that TL blocked the protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor-κB (NF-κB), IκBα, and mitogen-activated protein kinases (MAPKs). In the anti-inflammatory test, TL decreased the paw edema at the 5th h after λ-Carr administration in paw edema. We also demonstrated TL significantly attenuated the malondialdehyde (MDA) level in the edema paw at the 5th h after Carr injection. TL decreased the NO and TNF-α levels on the serum level at the 5th h after Carr injection. Western blotting revealed that TL decreased Carr-induced iNOS and COX-2 expressions at the 5th h in the edema paw. The anti-inflammatory mechanisms of TL might be related to the decrease in the level of iNOS, COX-2, IκBα, and MAPK pathway through the suppression of TNF-α, IL-1β, and IL-6.

scholarly journals Scaffolding Protein Gab2 Mediates Differentiation Signaling Downstream of Fms Receptor Tyrosine Kinase

2001 ◽  
Vol 21 (9) ◽  
pp. 3047-3056 ◽  
Author(s):  
Yan Liu ◽  
Brendan Jenkins ◽  
Jung Lim Shin ◽  
Larry R. Rohrschneider
Keyword(s):  
Tyrosine Kinase ◽  
Kinase Activity ◽  
Mapk Pathway ◽  
Growth Potential ◽  
Mitogen Activated Protein Kinase ◽  
Scaffolding Protein ◽  
Macrophage Differentiation ◽  
Mapk Activity ◽  
Mitogen Activated Protein ◽  
Macrophage Colony

ABSTRACT Fms is the receptor for macrophage colony-stimulating factor (M-CSF) and contains intrinsic tyrosine kinase activity. Expression of exogenous Fms in a murine myeloid progenitor cell line, FDC-P1 (FD-Fms), results in M-CSF-dependent growth and macrophage differentiation. Previously, we described a 100-kDa protein that was tyrosine phosphorylated upon M-CSF stimulation of FD-Fms cells. In this report, we identify this 100-kDa protein as the recently cloned scaffolding protein Gab2, and we demonstrate that Gab2 associates with several molecules involved in M-CSF signaling, including Grb2, SHP2, the p85 subunit of phosphatidylinositol 3′-kinase, SHIP, and SHC. Tyrosine phosphorylation of Gab2 in response to M-CSF requires the kinase activity of Fms, but not that of Src. Overexpression of Gab2 in FD-Fms cells enhanced both mitogen-activated protein kinase (MAPK) activity and macrophage differentiation, but reduced proliferation, in response to M-CSF. In contrast, a mutant of Gab2 that is unable to bind SHP2 did not potentiate MAPK activity. Furthermore, overexpression of this mutant in FD-Fms cells inhibited macrophage differentiation and resulted in a concomitant increase in growth potential in response to M-CSF. These data indicate that Gab2 is involved in the activation of the MAPK pathway and that the interaction between Gab2 and SHP2 is essential for the differentiation signal triggered by M-CSF.

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