Anti-Inflammatory Effects of Acupuncture at ST36 Point: A Literature Review in Animal Studies

So far, a number of acupuncture studies have shown anti-inflammatory effects of acupuncture treatment, mostly known at specific point ST36. However, there is no literature that oversaw the inflammation-regulatory effects of acupuncture in each tissue. Therefore, we investigated how acupuncture at specific acupoint ST36 regulates inflammation and its underlying mechanisms. We searched literatures on PubMed until July 2021 using the keywords “animal, acupuncture, ST36, inflammation, immune,” and 292 literatures were searched. We ultimately selected 69 studies to determine the anti-inflammatory actions of acupuncture at ST36 and classified the changes of inflammatory mediators according to target regions. Forty-three studies were included in body fluids, 27 studies in the digestive system, 17 studies in the nervous system, and 30 studies in other tissues or organs. In this review, we found that acupuncture at ST36 has clinical benefits in relieving inflammation through several mechanisms such as vagus nerve activation, toll-like receptor 4 (TLR4)/NF-κB signaling, macrophage polarization, mitogen-activated protein kinase (MAPK) signaling pathway, and cholinergic anti-inflammatory pathway. We expect that these data will inform further studies related to ST36 acupuncture on inflammation.

Download Full-text

Phosphorylation of Msx1 promotes cell proliferation through the Fgf9/18-MAPK signaling pathway during embryonic limb development

Nucleic Acids Research ◽

10.1093/nar/gkaa905 ◽

2020 ◽

Vol 48 (20) ◽

pp. 11452-11467

Author(s):

Yenan Yang ◽

Xiaoli Zhu ◽

Xiang Jia ◽

Wanwan Hou ◽

Guoqiang Zhou ◽

...

Keyword(s):

Cell Proliferation ◽

Limb Development ◽

Early Stage ◽

Control Cell ◽

Cell Lineage ◽

Mapk Signaling ◽

Mitogen Activated Protein Kinase ◽

Mitogen Activated Protein ◽

Embryonic Limb ◽

Underlying Mechanisms

Abstract Msh homeobox (Msx) is a subclass of homeobox transcriptional regulators that control cell lineage development, including the early stage of vertebrate limb development, although the underlying mechanisms are not clear. Here, we demonstrate that Msx1 promotes the proliferation of myoblasts and mesenchymal stem cells (MSCs) by enhancing mitogen-activated protein kinase (MAPK) signaling. Msx1 directly binds to and upregulates the expression of fibroblast growth factor 9 (Fgf9) and Fgf18. Accordingly, knockdown or antibody neutralization of Fgf9/18 inhibits Msx1-activated extracellular signal-regulated kinase 1/2 (Erk1/2) phosphorylation. Mechanistically, we determined that the phosphorylation of Msx1 at Ser136 is critical for enhancing Fgf9 and Fgf18 expression and cell proliferation, and cyclin-dependent kinase 1 (CDK1) is apparently responsible for Ser136 phosphorylation. Furthermore, mesenchymal deletion of Msx1/2 results in decreased Fgf9 and Fgf18 expression and Erk1/2 phosphorylation, which leads to serious defects in limb development in mice. Collectively, our findings established an important function of the Msx1-Fgf-MAPK signaling axis in promoting cell proliferation, thus providing a new mechanistic insight into limb development.

Download Full-text

JCPyV-Induced MAPK Signaling Activates Transcription Factors during Infection

International Journal of Molecular Sciences ◽

10.3390/ijms20194779 ◽

2019 ◽

Vol 20 (19) ◽

pp. 4779 ◽

Cited By ~ 2

Author(s):

Jeanne K. DuShane ◽

Colleen L. Mayberry ◽

Michael P. Wilczek ◽

Sarah L. Nichols ◽

Melissa S. Maginnis

Keyword(s):

Transcription Factors ◽

Mapk Signaling ◽

Mapk Cascade ◽

Mitogen Activated Protein Kinase ◽

Erk Pathway ◽

Downstream Signaling ◽

Dual Specificity ◽

Extracellular Signal ◽

Mitogen Activated Protein ◽

Underlying Mechanisms

JC polyomavirus (JCPyV), a ubiquitous human pathogen, is the etiological agent of the fatal neurodegenerative disease progressive multifocal leukoencephalopathy (PML). Like most viruses, JCPyV infection requires the activation of host-cell signaling pathways in order to promote viral replication processes. Previous works have established the necessity of the extracellular signal-regulated kinase (ERK), the terminal core kinase of the mitogen-activated protein kinase (MAPK) cascade (MAPK-ERK) for facilitating transcription of the JCPyV genome. However, the underlying mechanisms by which the MAPK-ERK pathway becomes activated and induces viral transcription are poorly understood. Treatment of cells with siRNAs specific for Raf and MAP kinase kinase (MEK) targets proteins in the MAPK-ERK cascade, significantly reducing JCPyV infection. MEK, the dual-specificity kinase responsible for the phosphorylation of ERK, is phosphorylated at times congruent with early events in the virus infectious cycle. Moreover, a MAPK-specific signaling array revealed that transcription factors downstream of the MAPK cascade, including cMyc and SMAD4, are upregulated within infected cells. Confocal microscopy analysis demonstrated that cMyc and SMAD4 shuttle to the nucleus during infection, and nuclear localization is reduced when ERK is inhibited. These findings suggest that JCPyV induction of the MAPK-ERK pathway is mediated by Raf and MEK and leads to the activation of downstream transcription factors during infection. This study further defines the role of the MAPK cascade during JCPyV infection and the downstream signaling consequences, illuminating kinases as potential therapeutic targets for viral infection.

Download Full-text

15-deoxy-Δ12,14-prostaglandin J2Down-Regulates Activin-Induced Activin Receptor, Smad, and Cytokines Expression via Suppression of NF-κB and MAPK Signaling in HepG2 Cells

PPAR Research ◽

10.1155/2013/751261 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7 ◽

Cited By ~ 2

Author(s):

Seung-Won Park ◽

Chunghee Cho ◽

Byung-Nam Cho ◽

Youngchul Kim ◽

Tae Won Goo ◽

...

Keyword(s):

Cell Proliferation ◽

Hepg2 Cells ◽

Mapk Pathway ◽

Mapk Signaling ◽

Activin A ◽

Mitogen Activated Protein Kinase ◽

Erk Phosphorylation ◽

Mitogen Activated Protein ◽

Regulatory Effects ◽

Activin Receptors

15-Deoxy-Δ12,14-prostaglandin J2(15d-PGJ2) and activin are implicated in the control of apoptosis, cell proliferation, and inflammation in cells. We examined both the mechanism by which 15d-PGJ2regulates the transcription of activin-induced activin receptors (ActR) and Smads in HepG2 cells and the involvement of the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways in this regulation. Activin A (25 ng/mL) inhibited HepG2 cell proliferation, whereas 15d-PGJ2(2 μM and 5 μM) had no effect. Activin A and 15d-PGJ2showed different regulatory effects on ActR and Smad expression, NF-κB p65 activity and MEK/ERK phosphorylation, whereas they both decreased IL-6 production and increased IL-8 production. When co-stimulated with 15d-PGJ2and activin, 15d-PGJ2inhibited the activin-induced increases in ActR and Smad expression, and decreased activin-induced IL-6 production. However, it increased activin-induced IL-8 production. In addition, 15d-PGJ2inhibited activin-induced NF-κB p65 activity and activin-induced MEK/ERK phosphorylation. These results suggest that 15d-PGJ2suppresses activin-induced ActR and Smad expression, down-regulates IL-6 production, and up-regulates IL-8 production via suppression of NF-κB and MAPK signaling pathway in HepG2 cells. Regulation of ActR and Smad transcript expression and cytokine production involves NF-κB and the MAPK pathway via interaction with 15d-PGJ2/activin/Smad signaling.

Download Full-text

Association of NF-κB and AP-1 with MMP-9 Overexpression in 2-Chloroethanol Exposed Rat Astrocytes

Cells ◽

10.3390/cells7080096 ◽

2018 ◽

Vol 7 (8) ◽

pp. 96 ◽

Cited By ~ 7

Author(s):

Tong Wang ◽

Xiaoxia Jin ◽

Yingjun Liao ◽

Qi Sun ◽

Chaohong Luo ◽

...

Keyword(s):

Signaling Pathway ◽

Nuclear Translocation ◽

Mapk Signaling ◽

Mitogen Activated Protein Kinase ◽

Activator Protein 1 ◽

Mitogen Activated Protein ◽

Rat Astrocytes ◽

Underlying Mechanisms ◽

Matrix Metalloproteinases 9 ◽

Pathological Consequence

Subacute poisoning of 1,2-dichloroethane (1,2-DCE) has become a serious occupational problem in China, and brain edema is its main pathological consequence, but little is known about the underlying mechanisms. As the metabolite of 1,2-DCE, 2-chloroethanol (2-CE) is more reactive, and might play an important role in the toxic effects of 1,2-DCE. In our previous studies, we found that matrix metalloproteinases-9 (MMP-9) expression was enhanced in mouse brains upon treatment with 1,2-DCE, and in rat astrocytes exposed to 2-CE. In the present study, we analyzed the association of nuclear factor kappa B (NF-κB) and activator protein-1 (AP-1) with MMP-9 overexpression in astrocytes treated with 2-CE. MMP-9, p65, c-Jun, and c-Fos were significantly upregulated by 2-CE treatment, which also enhanced phosphorylation of c-Jun, c-Fos and inhibitor of κBα (IκBα), and nuclear translocation of p65. Furthermore, inhibition of IκBα phosphorylation and AP-1 activity with the specific inhibitors could attenuate MMP-9 overexpression in the cells. On the other hand, inhibition of p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway suppressed the activation of both NF-κB and AP-1 in 2-CE-treated astrocytes. In conclusion, MMP-9 overexpression induced by 2-CE in astrocytes could be mediated at least in part through the p38 signaling pathway via activation of both NF-κB and AP-1. This study might provide novel clues for clarifying the mechanisms underlying 1,2-DCE associated cerebral edema.

Download Full-text

Chinese herbal formulas for postmenopausal osteoporosis: A review of preclinical evidence on animal studies and molecular mechanism

Traditional Medicine and Modern Medicine ◽

10.1142/s2575900018300023 ◽

2018 ◽

Vol 01 (02) ◽

pp. 75-83

Author(s):

Jing Lin ◽

Tian Lv ◽

Fubo Tian ◽

Yan Wang ◽

Mingyan Wang ◽

...

Keyword(s):

Postmenopausal Osteoporosis ◽

Animal Studies ◽

Mitogen Activated Protein Kinase ◽

Chinese Herbal ◽

Morphogenetic Protein ◽

Extracellular Signal ◽

Mitogen Activated Protein ◽

Underlying Mechanisms

Whether Chinese herbal formulas are effective in treatment of postmenopausal osteoporosis remains unclear. The aim of this study is to explore the experimental evidence of both in vitro and in vivo preclinical studies using Chinese herbal formulas in postmenopausal osteoporosis. Searches were applied to various databases with relevant keywords. Original in vivo and in vitro studies using Chinese herbal formulas to treat postmenopausal osteoporosis, and with full text available, were included. Er-Xian Decoction, Bu-Shen-Ning-Xin Decoction, Qing E Formula, Liuwei Dihuang Wan, and Xian-Ling-Gu-Bao Decoction, the most commonly studied formulas, were selected from the pool of Chinese medicine. The preclinical data indicated the potential use of Chinese herbal formulas in postmenopausal osteoporosis. The underlying mechanisms included bone morphogenetic protein (BMP), Wnt/[Formula: see text]-catenin, extracellular-signal-regulated kinase/c-Jun [Formula: see text] terminal kinase/mitogen-activated protein kinase (ERK/JNK/MAPK), estrogen receptor (ER), and osteoprotegerin/receptor activator of nuclear factor [Formula: see text]B ligand (OPG/RANKL) signaling pathways. This study demonstrated the anti-osteoporotic effect of Chinese herbal formulas targeting different pathways in bone metabolism. Further study with adequate sample size and follow-up time, appropriate controls, and optimal blinding is required.

Download Full-text

Ginsenoside Rg1 Downregulates the Shear Stress Induced MCP-1 Expression by Inhibiting MAPK Signaling Pathway

The American Journal of Chinese Medicine ◽

10.1142/s0192415x15500202 ◽

2015 ◽

Vol 43 (02) ◽

pp. 305-317 ◽

Cited By ~ 9

Author(s):

Jian He ◽

Yu-Lin Li

Keyword(s):

Shear Stress ◽

Mapk Pathway ◽

Inhibitory Effect ◽

Mapk Signaling ◽

Mitogen Activated Protein Kinase ◽

Ginsenoside Rg1 ◽

Negative Effects ◽

Specific Chemical ◽

Mitogen Activated Protein ◽

Anti Inflammatory

Ginsenoside Rg1 has been reported to possess anti-inflammatory activities, but the effects of Rg1 on the shear induced MCP-1 upregulation mechanism on endothelial cells (ECs) remain to be determined. In this study, we show that Rg1 down modulates shear induced pro-inflammatory cytokine MCP-1 gene expression and monocytes adhesion without potential cell toxicity. The negative effects on monocytes adhesion is due to a decrease in MCP-1 protein release. Furthermore, the inhibitory effect of Rg1 on the phosphorylation level of ERK, p38, and JNK mitogen-activated protein kinase (MAPK) induced by shear stress (SS) is similar with that of specific chemical inhibitors for MAPK pathways activation. These results demonstrate that ginsenoside Rg1 inhibits the shear induced inflammation by suppressing the MAPK pathway. This suggests that Rg1 may serve as a novel anti-inflammatory agent for inflammation-induced cardiovascular diseases treatment.

Download Full-text

Targeting MAPK Signaling in Age-Related Macular Degeneration

Ophthalmology and Eye Diseases ◽

10.4137/oed.s32200 ◽

2016 ◽

Vol 8 ◽

pp. OED.S32200 ◽

Cited By ~ 19

Author(s):

Svetlana V. Kyosseva

Keyword(s):

Oxidative Stress ◽

Macular Degeneration ◽

Animal Studies ◽

Mapk Signaling ◽

Age Related Macular Degeneration ◽

Mitogen Activated Protein Kinase ◽

Age Related ◽

Mitogen Activated Protein ◽

Extracellular Stimuli ◽

Mapk Inhibitors

Age-related macular degeneration (AMD) is a major cause of irreversible blindness affecting elderly people in the world. AMD is a complex multifactorial disease associated with demographic, genetics, and environmental risk factors. It is well established that oxidative stress, inflammation, and apoptosis play critical roles in the pathogenesis of AMD. The mitogen-activated protein kinase (MAPK) signaling pathways are activated by diverse extracellular stimuli, including growth factors, mitogens, hormones, cytokines, and different cellular stressors such as oxidative stress. They regulate cell proliferation, differentiation, survival, and apoptosis. This review addresses the novel findings from human and animal studies on the relationship of MAPK signaling with AMD. The use of specific MAPK inhibitors may represent a potential therapeutic target for the treatment of this debilitating eye disease.

Download Full-text

Dexamethasone enhances CD163 expression in porcine IPKM immortalized macrophages

In Vitro Cellular & Developmental Biology - Animal ◽

10.1007/s11626-020-00535-5 ◽

2021 ◽

Vol 57 (1) ◽

pp. 10-16

Author(s):

Takato Takenouchi ◽

Takeya Morozumi ◽

Emi Wada ◽

Shunichi Suzuki ◽

Yasutaka Nishiyama ◽

...

Keyword(s):

Scavenger Receptor ◽

Mapk Signaling ◽

Mitogen Activated Protein Kinase ◽

Respiratory Syndrome Virus ◽

Phenotypic Marker ◽

Putative Receptor ◽

Cd163 Expression ◽

Mitogen Activated Protein ◽

Anti Inflammatory

AbstractIn our previous study, we established a unique porcine macrophage cell line, immortalized porcine kidney-derived macrophages (IPKM). The purpose of the present study was to further elucidate the characteristics of IPKM. CD163 is a scavenger receptor for the hemoglobin-haptoglobin complex and is used as a phenotypic marker of anti-inflammatory M2 macrophages. The expression of CD163 is enhanced by dexamethasone (DEX), a potent steroidal anti-inflammatory drug, in human and rodent macrophages in vitro. Therefore, we investigated the effects of DEX on CD163 expression in porcine IPKM. Treatment with DEX markedly enhanced CD163 expression in the IPKM. In addition, we found that SB203580, a selective inhibitor of p38 mitogen-activated protein kinase (MAPK), blocked the effects of DEX, suggesting that the p38 MAPK signaling pathway is involved in the regulation of the DEX-induced enhancement of CD163 expression. Since CD163 is considered to be a putative receptor for the porcine reproductive and respiratory syndrome virus (PRRSV), the effects of DEX on the infection of IPKM by PRRSV were evaluated. Although the IPKM were susceptible to infection by the Fostera PRRSV vaccine strain, DEX treatment did not affect the propagation of the virus in the IPKM. This suggests that the DEX-induced enhancement of CD163 expression alone is not sufficient to facilitate the infection of IPKM by PRRSV.

Download Full-text

Specific Functional Features of the Cell Integrity MAP Kinase Pathway in the Dimorphic Fission Yeast Schizosaccharomyces japonicus

Journal of Fungi ◽

10.3390/jof7060482 ◽

2021 ◽

Vol 7 (6) ◽

pp. 482

Author(s):

Elisa Gómez-Gil ◽

Alejandro Franco ◽

Beatriz Vázquez-Marín ◽

Francisco Prieto-Ruiz ◽

Armando Pérez-Díaz ◽

...

Keyword(s):

Fission Yeast ◽

Environmental Changes ◽

Yeast Species ◽

Mapk Signaling ◽

Fine Tuning ◽

Mitogen Activated Protein Kinase ◽

Major Influence ◽

Cell Integrity ◽

Mitogen Activated Protein ◽

Functional Features

Mitogen activated protein kinase (MAPK) signaling pathways execute essential functions in eukaryotic organisms by transducing extracellular stimuli into adaptive cellular responses. In the fission yeast model Schizosaccharomyces pombe the cell integrity pathway (CIP) and its core effector, MAPK Pmk1, play a key role during regulation of cell integrity, cytokinesis, and ionic homeostasis. Schizosaccharomyces japonicus, another fission yeast species, shows remarkable differences with respect to S. pombe, including a robust yeast to hyphae dimorphism in response to environmental changes. We show that the CIP MAPK module architecture and its upstream regulators, PKC orthologs Pck1 and Pck2, are conserved in both fission yeast species. However, some of S. pombe’s CIP-related functions, such as cytokinetic control and response to glucose availability, are regulated differently in S. japonicus. Moreover, Pck1 and Pck2 antagonistically regulate S. japonicus hyphal differentiation through fine-tuning of Pmk1 activity. Chimeric MAPK-swapping experiments revealed that S. japonicus Pmk1 is fully functional in S. pombe, whereas S. pombe Pmk1 shows a limited ability to execute CIP functions and promote S. japonicus mycelial development. Our findings also suggest that a modified N-lobe domain secondary structure within S. japonicus Pmk1 has a major influence on the CIP signaling features of this evolutionarily diverged fission yeast.

Download Full-text

Thymoquinone, a Dietary Bioactive Compound, Exerts Anti-Inflammatory Effects in Colitis by Stimulating Expression of the Colonic Epithelial PPAR-γ Transcription Factor

Nutrients ◽

10.3390/nu13041343 ◽

2021 ◽

Vol 13 (4) ◽

pp. 1343

Author(s):

Balaji Venkataraman ◽

Saeeda Almarzooqi ◽

Vishnu Raj ◽

Abdullah T. Alhassani ◽

Ahmad S. Alhassani ◽

...

Keyword(s):

Transcription Factor ◽

Activity Index ◽

Nigella Sativa ◽

Mapk Signaling ◽

Mitogen Activated Protein Kinase ◽

Ppar Γ ◽

Anti Inflammatory ◽

Ht 29

Inflammatory bowel diseases (IBD) are chronic inflammatory disorders with increasing incidence and prevalence worldwide. Here, we investigated thymoquinone (TQ), a naturally occurring phytochemical present in Nigella sativa, for anti-inflammatory effects in colonic inflammation. To address this, we used in vivo (mice) and in vitro (HT-29 cells) models in this investigation. Our results showed that TQ treatment significantly reduced the disease activity index (DAI), myeloperoxidase (MPO) activity, and protected colon microscopic architecture. In addition, TQ also reduced the expression of proinflammatory cytokines and mediators at both the mRNA and protein levels. Further, TQ decreased phosphorylation of the activated mitogen-activated protein kinase (MAPK) signaling pathway and nuclear factor kappa B (NF-κB) proteins and enhanced colon epithelial PPAR-γ transcription factor expression. TQ significantly decreased proinflammatory chemokines (CXCL-1 and IL-8), and mediator (COX-2) mRNA expression in HT-29 cells treated with TNF-α. TQ also increased HT-29 PPAR-γ mRNA, PPAR-γ protein expression, and PPAR-γ promoter activity. These results indicate that TQ inhibits MAPK and NF-κB signaling pathways and transcriptionally regulates PPAR-γ expression to induce potent anti-inflammatory activity in vivo and in vitro models of colon inflammation.

Download Full-text