scholarly journals The Emerging Role of Macrophages in Immune System Dysfunction under Real and Simulated Microgravity Conditions

2021 ◽  
Vol 22 (5) ◽  
pp. 2333
Author(s):  
Yulong Sun ◽  
Yuanyuan Kuang ◽  
Zhuo Zuo
Keyword(s):  
Immune System ◽  
Mapk Signaling ◽  
Immune Defense ◽  
Mitogen Activated Protein Kinase ◽  
Therapeutic Drugs ◽  
Physiological Processes ◽  
Immune System Dysfunction ◽  
Cell Immunity ◽  
Mitogen Activated Protein ◽  
Microgravity Conditions

In the process of exploring space, the astronaut’s body undergoes a series of physiological changes. At the level of cellular behavior, microgravity causes significant alterations, including bone loss, muscle atrophy, and cardiovascular deconditioning. At the level of gene expression, microgravity changes the expression of cytokines in many physiological processes, such as cell immunity, proliferation, and differentiation. At the level of signaling pathways, the mitogen-activated protein kinase (MAPK) signaling pathway participates in microgravity-induced immune malfunction. However, the mechanisms of these changes have not been fully elucidated. Recent studies suggest that the malfunction of macrophages is an important breakthrough for immune disorders in microgravity. As the first line of immune defense, macrophages play an essential role in maintaining homeostasis. They activate specific immune responses and participate in large numbers of physiological activities by presenting antigen and secreting cytokines. The purpose of this review is to summarize recent advances on the dysfunction of macrophages arisen from microgravity and to discuss the mechanisms of these abnormal responses. Hopefully, our work will contribute not only to the future exploration on the immune system in space, but also to the development of preventive and therapeutic drugs against the physiological consequences of spaceflight.

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

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.

scholarly journals Effect of Static Magnetic Field on Monascus ruber M7 Based on Transcriptome Analysis

2021 ◽  
Vol 7 (4) ◽  
pp. 256
Author(s):  
Shuyan Yang ◽  
Hongyi Zhou ◽  
Weihua Dai ◽  
Juan Xiong ◽  
Fusheng Chen
Keyword(s):  
Magnetic Field ◽  
Static Magnetic Field ◽  
Morphological Characteristics ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Primary Metabolism ◽  
Monascus Ruber ◽  
Growing Period ◽  
Monascus Pigments ◽  
Mitogen Activated Protein

The effects of a static magnetic field (SMF) on Monascus ruber M7 (M. ruber M7) cultured on potato dextrose agar (PDA) plates under SMF treatment at different intensities (5, 10, and 30 mT) were investigated in this paper. The results revealed that, compared with the control (CK, no SMF treatment), the SMF at all tested intensities did not significantly influence the morphological characteristics of M. ruber M7, while the intracellular and extracellular Monascus pigments (MPs) and extracellular citrinin (CIT) of M. ruber M7 were increased at 10 and 30 mT SMF but there was no impact on the MPs and CIT at 5 mT SMF. The transcriptome data of M. ruber M7 cultured at 30 mT SMF on PDA for 3 and 7 d showed that the SMF could increase the transcriptional levels of some relative genes with the primary metabolism, including the carbohydrate metabolism, amino acid metabolism, and lipid metabolism, especially in the early growing period (3 d). SMF could also affect the transcriptional levels of the related genes to the biosynthetic pathways of MPs, CIT, and ergosterol, and improve the transcription of the relative genes in the mitogen-activated protein kinase (MAPK) signaling pathway of M. ruber M7. These findings provide insights into a comprehensive understanding of the effects of SMF on filamentous fungi.

scholarly journals Topical Spilanthol Inhibits MAPK Signaling and Ameliorates Allergic Inflammation in DNCB-Induced Atopic Dermatitis in Mice

2019 ◽  
Vol 20 (10) ◽  
pp. 2490 ◽  
Author(s):  
Wen-Chung Huang ◽  
Chun-Hsun Huang ◽  
Sindy Hu ◽  
Hui-Ling Peng ◽  
Shu-Ju Wu
Keyword(s):  
Atopic Dermatitis ◽  
Mast Cells ◽  
Protein Kinase ◽  
Allergic Inflammation ◽  
Skin Lesions ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Mapk Pathways ◽  
Mitogen Activated Protein ◽  
Cox 2

Atopic dermatitis (AD) is a recurrent allergic skin disease caused by genetic and environmental factors. Patients with AD may experience immune imbalance, increased levels of mast cells, immunoglobulin (Ig) E and pro-inflammatory factors (Cyclooxygenase, COX-2 and inducible NO synthase, iNOS). While spilanthol (SP) has anti-inflammatory and analgesic activities, its effect on AD remains to be explored. To develop a new means of SP, inflammation-related symptoms of AD were alleviated, and 2,4-dinitrochlorobenzene (DNCB) was used to induce AD-like skin lesions in BALB/c mice. Histopathological analysis was used to examine mast cells and eosinophils infiltration in AD-like skin lesions. The levels of IgE, IgG1 and IgG2a were measured by enzyme-linked immunosorbent assay (ELISA) kits. Western blot was used for analysis of the mitogen-activated protein kinase (MAPK) pathways and COX-2 and iNOS protein expression. Topical SP treatment reduced serum IgE and IgG2a levels and suppressed COX-2 and iNOS expression via blocked mitogen-activated protein kinase (MAPK) pathways in DNCB-induced AD-like lesions. Histopathological examination revealed that SP reduced epidermal thickness and collagen accumulation and inhibited mast cells and eosinophils infiltration into the AD-like lesions skin. These results indicate that SP may protect against AD skin lesions through inhibited MAPK signaling pathways and may diminish the infiltration of inflammatory cells to block allergic inflammation.

scholarly journals Bacillus anthracis Spores Stimulate Cytokine and Chemokine Innate Immune Responses in Human Alveolar Macrophages through Multiple Mitogen-Activated Protein Kinase Pathways

2006 ◽  
Vol 74 (8) ◽  
pp. 4430-4438 ◽  
Author(s):  
Kaushik Chakrabarty ◽  
Wenxin Wu ◽  
J. Leland Booth ◽  
Elizabeth S. Duggan ◽  
K. Mark Coggeshall ◽  
...  
Keyword(s):  
Immune System ◽  
Bacillus Anthracis ◽  
Alveolar Macrophages ◽  
Innate Immune System ◽  
Innate Immune ◽  
Mitogen Activated Protein Kinase ◽  
Tnf Α ◽  
Human Alveolar Macrophages ◽  
Mitogen Activated Protein ◽  
Multiple Signaling

ABSTRACT Contact with the human alveolar macrophage plays a key role in the innate immune response to Bacillus anthracis spores. Because there is a significant delay between the initial contact of the spore with the host and clinical evidence of disease, there appears to be temporary containment of the pathogen by the innate immune system. Therefore, the early macrophage response to Bacillus anthracis exposure is important in understanding the pathogenesis of this disease. In this paper, we studied the initial events after exposure to spores, beginning with the rapid internalization of spores by the macrophages. Spore exposure rapidly activated the mitogen-activated protein kinase signaling pathways extracellular signal-regulated kinase, c-Jun-NH2-terminal kinase, and p38. This was followed by the transcriptional activation of cytokine and primarily monocyte chemokine genes as determined by RNase protection assays. Transcriptional induction is reflected at the translational level, as interleukin-1α (IL-1α), IL-1β, IL-6, and tumor necrosis factor alpha (TNF-α) cytokine protein levels were markedly elevated as determined by enzyme-linked immunosorbent assay. Induction of IL-6 and TNF-α, and, to a lesser extent, IL-1α and IL-1β, was partially inhibited by the blockade of individual mitogen-activated protein kinases, while the complete inhibition of cytokine induction was achieved when multiple signaling pathway inhibitors were used. Taken together, these data clearly show activation of the innate immune system in human alveolar macrophages by Bacillus anthracis spores. The data also show that multiple signaling pathways are involved in this cytokine response. This report is the first comprehensive examination of this process in primary human alveolar macrophages.

scholarly journals Platyphyllenone Induces Autophagy and Apoptosis by Modulating the AKT and JNK Mitogen-Activated Protein Kinase Pathways in Oral Cancer Cells

2021 ◽  
Vol 22 (8) ◽  
pp. 4211
Author(s):  
Yen-Tze Liu ◽  
Hsin-Yu Ho ◽  
Chia-Chieh Lin ◽  
Yi-Ching Chuang ◽  
Yu-Sheng Lo ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Oral Cancer ◽  
Protein Expression ◽  
Caspase 3 ◽  
Therapeutic Option ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Dependent Manner ◽  
Cancer Proliferation ◽  
Mitogen Activated Protein

Platyphyllenone is a type of diarylheptanoid that exhibits anti-inflammatory and chemoprotective effects. However, its effect on oral cancer remains unclear. In this study, we investigated whether platyphyllenone can promote apoptosis and autophagy in SCC-9 and SCC-47 cells. We found that it dose-dependently promoted the cleavage of PARP; caspase-3, -8, and -9 protein expression; and also led to cell cycle arrest at the G2/M phase. Platyphyllenone up-regulated LC3-II and p62 protein expression in both SCC-9 and SCC-47 cell lines, implying that it can induce autophagy. Furthermore, the results demonstrated that platyphyllenone significantly decreased p-AKT and increased p-JNK1/2 mitogen-activated protein kinase (MAPK) signaling pathway in a dose-dependent manner. The specific inhibitors of p-JNK1/2 also reduced platyphyllenone-induced cleavage of PARP, caspase-3, and caspase -8, LC3-II and p62 protein expression. These findings are the first to demonstrate that platyphyllenone can induce both autophagy and apoptosis in oral cancers, and it is expected to provide a therapeutic option as a chemopreventive agent against oral cancer proliferation.

scholarly journals BRAF mutation in hairy cell leukemia

2014 ◽  
Author(s):  
Ahmad Ahmadzadeh ◽  
Saeid Shahrabi ◽  
Kaveh Jaseb ◽  
Fatemeh Norozi ◽  
Mohammad Shahjahani ◽  
...  
Keyword(s):  
B Cell ◽  
Hairy Cell Leukemia ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Braf V600e ◽  
Common Mutation ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Mitogen Activated Protein ◽  
Almost All

BRAF is a serine/threonine kinase with a regulatory role in the mitogen-activated protein kinase (MAPK) signaling pathway. A mutation in the RAF gene, especially in BRAF protein, leads to an increased stimulation of this cascade, causing uncontrolled cell division and development of malignancy. Several mutations have been observed in the gene coding for this protein in a variety of human malignancies, including hairy cell leukemia (HCL). BRAF V600E is the most common mutation reported in exon15 of BRAF, which is observed in almost all cases of classic HCL, but it is negative in other B-cell malignancies, including the HCL variant. Therefore it can be used as a marker to differentiate between these B-cell disorders. We also discuss the interaction between miRNAs and signaling pathways, including MAPK, in HCL. When this mutation is present, the use of BRAF protein inhibitors may represent an effective treatment. In this review we have evaluated the role of the mutation of the BRAF gene in the pathogenesis and progression of HCL.

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 Selective expression of the scaffold protein JSAP1 in spermatogonia and spermatocytes

Reproduction ◽  
2006 ◽  
Vol 131 (4) ◽  
pp. 711-719 ◽  
Author(s):  
Munkhuu Bayarsaikhan ◽  
Akiko Shiratsuchi ◽  
Davaakhuu Gantulga ◽  
Yoshinobu Nakanishi ◽  
Katsuji Yoshioka
Keyword(s):  
Protein Kinase ◽  
Western Blotting ◽  
Cell Types ◽  
Mapk Signaling ◽  
Scaffold Protein ◽  
Mitogen Activated Protein Kinase ◽  
Interacting Protein ◽  
Early Postnatal Development ◽  
Mitogen Activated Protein ◽  
Signaling Modules

Scaffold proteins of mitogen-activated protein kinase (MAPK) intracellular signal transduction pathways mediate the efficient and specific activation of the relevant MAPK signaling modules. Previously, our group and others have identified c-Jun NH2-terminal kinase (JNK)/stress-activated protein kinase-associated protein 1 (JSAP1, also known as JNK-interacting protein 3) as a scaffold protein for JNK MAPK pathways. Although JSAP1 is expressed in the testis in adults, its expression during development has not been investigated. In addition, it is unknown which types of cells in the testis express the scaffold protein. Here, we examined the expression of JSAP1 in the testis of mice aged 14 days, 20 days, 6 weeks, and 12 weeks by immunohistochemistry and Western blotting. The specificity of the anti-JSAP1 antibody was evaluated from its reactivity to exogenously expressed JSAP1 and a structurally related protein, and by antigen-absorption experiments. The immunohistochemical analyses with the specific antibody showed that the JSAP1 protein was selectively expressed in the spermatogonia and spermatocytes, but not in other cell types, including spermatids and somatic cells, during development. However, not all spermatogonia and spermatocytes were immunopositive either, especially in the 12-week-old mouse testis. Furthermore, we found by Western blotting that the expression levels of JSAP1 protein vary during development; there is high expression until 6 weeks after birth, which approximately corresponds to the end of the first wave of spermatogenesis. Collectively, these results suggest that JSAP1 function may be important in spermatogenic cells during early postnatal development.

scholarly journals APPL1 mediates adiponectin-stimulated p38 MAPK activation by scaffolding the TAK1-MKK3-p38 MAPK pathway

2011 ◽  
Vol 300 (1) ◽  
pp. E103-E110 ◽  
Author(s):  
Xiaoban Xin ◽  
Lijun Zhou ◽  
Caleb M. Reyes ◽  
Feng Liu ◽  
Lily Q. Dong
Keyword(s):  
Protein Kinase ◽  
P38 Mapk ◽  
Mapk Pathway ◽  
Adaptor Protein ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Scaffolding Protein ◽  
Mapk Activation ◽  
P38 Mapk Pathway ◽  
Mitogen Activated Protein

The adaptor protein APPL1 mediates the stimulatory effect of adiponectin on p38 mitogen-activated protein kinase (MAPK) signaling, yet the underlying mechanism remains unclear. Here we show that, in C2C12 cells, overexpression or suppression of APPL1 enhanced or suppressed, respectively, adiponectin-stimulated p38 MAPK upstream kinase cascade, consisting of transforming growth factor-β-activated kinase 1 (TAK1) and mitogen-activated protein kinase kinase 3 (MKK3). In vitro affinity binding and coimmunoprecipitation experiments revealed that TAK1 and MKK3 bind to different regions of APPL1, suggesting that APPL1 functions as a scaffolding protein to facilitate adiponectin-stimulated p38 MAPK activation. Interestingly, suppressing APPL1 had no effect on TNFα-stimulated p38 MAPK phosphorylation in C2C12 myotubes, indicating that the stimulatory effect of APPL1 on p38 MAPK activation is selective. Taken together, our study demonstrated that the TAK1-MKK3 cascade mediates adiponectin signaling and uncovers a scaffolding role of APPL1 in regulating the TAK1-MKK3-p38 MAPK pathway, specifically in response to adiponectin stimulation.

scholarly journals Vaccinia-Related Kinase 2 Modulates the Stress Response to Hypoxia Mediated by TAK1

2007 ◽  
Vol 27 (20) ◽  
pp. 7273-7283 ◽  
Author(s):  
Sandra Blanco ◽  
Claudio Santos ◽  
Pedro A. Lazo
Keyword(s):  
Stress Response ◽  
Cellular Response ◽  
Mapk Signaling ◽  
Cellular Stress Response ◽  
Mitogen Activated Protein Kinase ◽  
Stable Complex ◽  
Intracellular Proteins ◽  
Mitogen Activated Protein ◽  
Jnk Activation ◽  
Protein Kinase Kinase

ABSTRACT Hypoxia represents a major stress that requires an immediate cellular response in which different signaling pathways participate. Hypoxia induces an increase in the activity of TAK1, an atypical mitogen-activated protein kinase kinase kinase (MAPKKK), which responds to oxidative stress by triggering cascades leading to the activation of c-Jun N-terminal kinase (JNK). JNK activation by hypoxia requires assembly with the JIP1 scaffold protein, which might also interact with other intracellular proteins that are less well known but that might modulate MAPK signaling. We report that TAK1 is able to form a stable complex with JIP1 and thus regulate the activation of JNK, which in turn determines the cellular stress response to hypoxia. This activation of TAK1-JIP1-JNK is suppressed by vaccinia-related kinase 2 (VRK2). VRK2A is able to interact with TAK1 by its C-terminal region, forming stable complexes. The kinase activity of VRK2 is not necessary for this interaction or the downregulation of AP1-dependent transcription. Furthermore, reduction of the endogenous VRK2 level with short hairpin RNA can increase the response induced by hypoxia, suggesting that the intracellular levels of VRK2 can determine the magnitude of this stress response.

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