scholarly journals Induction of CEMIP in Chondrocytes by Inflammatory Cytokines: Underlying Mechanisms and Potential Involvement in Osteoarthritis

2020 ◽  
Vol 21 (9) ◽  
pp. 3140
Author(s):  
Takashi Ohtsuki ◽  
Omer F. Hatipoglu ◽  
Keiichi Asano ◽  
Junko Inagaki ◽  
Keiichiro Nishida ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Regulatory Mechanism ◽  
Nuclear Translocation ◽  
Mechanical Strain ◽  
Molecular Size ◽  
Underlying Mechanism ◽  
Erk Activation ◽  
Related Molecule ◽  
Underlying Mechanisms ◽  
And Cartilage

In patients with osteoarthritis (OA), there is a decrease in both the concentration and molecular size of hyaluronan (HA) in the synovial fluid and cartilage. Cell migration-inducing hyaluronidase 1 (CEMIP), also known as hyaluronan (HA)-binding protein involved in HA depolymerization (HYBID), was recently reported as an HA depolymerization-related molecule expressed in the cartilage of patients with OA. However, the underlying mechanism of CEMIP regulation is not well understood. We found that CEMIP expression was transiently increased by interleukine-1β (IL-1β) stimulation in chondrocytic cells. We also observed that ERK activation and NF-κB nuclear translocation were involved in the induction of CEMIP by IL-1β. In addition, both administration of HA and mechanical strain attenuated the CEMIP induction in IL-1β-stimulated chondrocytes. In conclusion, we clarified the regulatory mechanism of CEMIP in chondrocytes by inflammatory cytokines and suggested the potential involvement in osteoarthritis development.

scholarly journals Menaquinone-4 Suppresses Lipopolysaccharide-Induced Inflammation in MG6 Mouse Microglia-Derived Cells by Inhibiting the NF-κB Signaling Pathway

2019 ◽  
Vol 20 (9) ◽  
pp. 2317 ◽  
Author(s):  
Wahyu Dwi Saputra ◽  
Nao Aoyama ◽  
Michio Komai ◽  
Hitoshi Shirakawa
Keyword(s):  
Inflammatory Cytokines ◽  
Nuclear Translocation ◽  
Mrna Level ◽  
Underlying Mechanism ◽  
Inflammatory Reactions ◽  
Cell Responses ◽  
Tnf Α ◽  
The Central Nervous System ◽  
The Brain ◽  
Microglial Inflammation

The overactivation of microglia is known to trigger inflammatory reactions in the central nervous system, which ultimately induce neuroinflammatory disorders including Alzheimer’s disease. However, increasing evidence has shown that menaquinone-4 (MK-4), a subtype of vitamin K2, can attenuate inflammation in the peripheral system. Whereas it was also observed at high levels within the brain, its function in this organ has not been well characterized. Therefore, we investigated the effect of MK-4 on microglial activation and clarified the underlying mechanism. Mouse microglia-derived MG6 cells were exposed to lipopolysaccharide (LPS) either with or without MK-4 pretreatment. Cell responses with respect to inflammatory cytokines (Il-1β, Tnf-α, and Il-6) were measured by qRT-PCR. We further analyzed the phosphorylation of TAK1, IKKα/β, and p65 of the NF-κB subunit by Western blotting. We observed that in LPS-induced MG6 cells, MK-4 dose-dependently suppressed the upregulation of inflammatory cytokines at the mRNA level. It also significantly decreased the phosphorylation of p65, but did not affect that TAK1 and IKKα/β. Furthermore, the nuclear translocation of NF-κB in LPS-induced MG6 cells was inhibited by MK-4. These results indicate that MK-4 attenuates microglial inflammation by inhibiting NF-κB signaling.

Cytokine synergy, collagenases and cartilage collagen breakdown

2003 ◽  
Vol 70 ◽  
pp. 125-133 ◽  
Author(s):  
Tim E. Cawston ◽  
Jenny M. Milner ◽  
Jon B. Catterall ◽  
Andrew D. Rowan
Keyword(s):  
Matrix Metalloproteinases ◽  
Inflammatory Cytokines ◽  
Activator Protein 1 ◽  
Activator Protein ◽  
And Cartilage ◽  
Pro Inflammatory Cytokines

We have investigated proteinases that degrade cartilage collagen. We show that pro-inflammatory cytokines act synergistically with oncastatin M to promote cartilage collagen resorption by the up-regulation and activation of matrix metalloproteinases (MMPs). The precise mechanisms are not known, but involve the up-regulation of c-fos, which binds to MMP promoters at a proximal activator protein-1 (AP-1) site. This markedly up-regulates transcription and leads to higher levels of active MMP proteins.

Contrasting underlying mechanisms of different barrier coating types

TAPPI Journal ◽  
2018 ◽  
Vol 17 (01) ◽  
pp. 31-37
Author(s):  
Bryan McCulloch ◽  
John Roper ◽  
Kaitlin Rosen
Keyword(s):  
Food Packaging ◽  
Underlying Mechanism ◽  
Consumer Products ◽  
Mechanical Degradation ◽  
Design Rules ◽  
Barrier Coatings ◽  
Barrier Materials ◽  
Barrier Coating ◽  
Coating Type ◽  
Underlying Mechanisms

Barrier coatings are used in applications including food packaging, dry goods, and consumer products to prevent transport of different compounds either through or into paper and paperboard substrates. These coatings are useful in packaging to contain active ingredients, such as fragrances, or to protect contents from detrimental substances, such as oxygen, water, grease, or other chemicals of concern. They also are used to prevent visual changes or mechanical degradation that might occur if the paper becomes saturated. The performance and underlying mechanism depends on the barrier coating type and, in particular, on whether the barrier coating is designed to prevent diffusive or capillary transport. Estimates on the basis of fundamental transport phenomena and data from a broad screening of different barrier materials can be used to understand the limits of various approaches to construct barrier coatings. These estimates also can be used to create basic design rules for general classes of barrier coatings.

scholarly journals IGF-1 Haploinsufficiency Causes Age-Related Chronic Cochlear Inflammation and Increases Noise-Induced Hearing Loss

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1686
Author(s):  
Adelaida M. Celaya ◽  
Lourdes Rodríguez-de la Rosa ◽  
Jose M. Bermúdez-Muñoz ◽  
José M. Zubeldia ◽  
Carlos Romá-Mateo ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Inflammatory Cytokines ◽  
Noise Exposure ◽  
Sensorineural Deafness ◽  
Serum Levels ◽  
Genetic Syndromes ◽  
Expression Ratio ◽  
Postnatal Maturation ◽  
Age Related ◽  
Underlying Mechanisms

Insulin-like growth factor 1 (IGF-1) deficiency is an ultrarare syndromic human sensorineural deafness. Accordingly, IGF-1 is essential for the postnatal maturation of the cochlea and the correct wiring of hearing in mice. Less severe decreases in human IGF-1 levels have been associated with other hearing loss rare genetic syndromes, as well as with age-related hearing loss (ARHL). However, the underlying mechanisms linking IGF-1 haploinsufficiency with auditory pathology and ARHL have not been studied. Igf1-heterozygous mice express less Igf1 transcription and have 40% lower IGF-1 serum levels than wild-type mice. Along with ageing, IGF-1 levels decreased concomitantly with the increased expression of inflammatory cytokines, Tgfb1 and Il1b, but there was no associated hearing loss. However, noise exposure of these mice caused increased injury to sensory hair cells and irreversible hearing loss. Concomitantly, there was a significant alteration in the expression ratio of pro- and anti-inflammatory cytokines in Igf1+/− mice. Unbalanced inflammation led to the activation of the stress kinase JNK and the failure to activate AKT. Our data show that IGF-1 haploinsufficiency causes a chronic subclinical proinflammatory age-associated state and, consequently, greater susceptibility to stressors. This work provides the molecular bases to further understand hearing disorders linked to IGF-1 deficiency.

scholarly journals Anti-Inflammatory Activities of a Chinese Herbal Formula IBS-20In VitroandIn Vivo

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Zhonghan Yang ◽  
Viktoriya Grinchuk ◽  
Siu Po Ip ◽  
Chun-Tao Che ◽  
Harry H. S. Fong ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Symptom Relief ◽  
Herbal Extract ◽  
Beneficial Effects ◽  
Inflammatory Bowel ◽  
Anti Inflammatory ◽  
Underlying Mechanisms ◽  
Irritable Bowel ◽  
Nitric Oxide Synthase 2 ◽  
Oxide Synthase

Irritable bowel syndrome (IBS) is a functional bowel disorder and the etiology is not well understood. Currently there is no cure for IBS and no existing medication induces symptom relief in all patients. IBS-20 is a 20-herb Chinese medicinal formula that offers beneficial effects in patients with IBS; however, the underlying mechanisms are largely unknown. This study showed that IBS-20 potently inhibited LPS- or IFNΓ-stimulated expression of pro-inflammatory cytokines, as well as classically activated macrophage marker nitric oxide synthase 2. Similarly, IBS-20 or the component herbCoptis chinensisdecreased LPS-stimulated pro-inflammatory cytokine secretion from JAWS II dendritic cells. IBS-20 or the component herbs also blocked or attenuated the IFNΓ-induced drop in transepithelial electric resistance, an index of permeability, in fully differentiated Caco-2 monolayer. Finally, the up-regulation of key inflammatory cytokines in inflamed colon from TNBS-treated mice was suppressed significantly by orally administrated IBS-20, including IFNΓ and IL-12p40. These data indicate that the anti-inflammatory activities of IBS-20 may contribute to the beneficial effects of the herbal extract in patients with IBS, providing a potential mechanism of action for IBS-20. In addition, IBS-20 may be a potential therapeutic agent against other Th1-dominant gut pathologies such as inflammatory bowel disease.

scholarly journals Recent Advances in Application of Biosensors in Tissue Engineering

2014 ◽  
Vol 2014 ◽  
pp. 1-18 ◽  
Author(s):  
Anwarul Hasan ◽  
Md Nurunnabi ◽  
Mahboob Morshed ◽  
Arghya Paul ◽  
Alessandro Polini ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Cell Culture ◽  
Small Molecules ◽  
Real Time ◽  
Inflammatory Cytokines ◽  
Serum Proteins ◽  
Molecular Size ◽  
Medical Diagnostics ◽  
Alpha Fetoprotein ◽  
Pharmaceutical Industries

Biosensors research is a fast growing field in which tens of thousands of papers have been published over the years, and the industry is now worth billions of dollars. The biosensor products have found their applications in numerous industries including food and beverages, agricultural, environmental, medical diagnostics, and pharmaceutical industries and many more. Even though numerous biosensors have been developed for detection of proteins, peptides, enzymes, and numerous other biomolecules for diverse applications, their applications in tissue engineering have remained limited. In recent years, there has been a growing interest in application of novel biosensors in cell culture and tissue engineering, for example, real-time detection of small molecules such as glucose, lactose, and H2O2as well as serum proteins of large molecular size, such as albumin and alpha-fetoprotein, and inflammatory cytokines, such as IFN-g and TNF-α. In this review, we provide an overview of the recent advancements in biosensors for tissue engineering applications.

scholarly journals HMGB1 Mediated Inflammation and Autophagy Contribute to Endometriosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Jingying Huang ◽  
Xuan Chen ◽  
Yuchun Lv
Keyword(s):  
Western Blotting ◽  
Inflammatory Cytokines ◽  
Expression Patterns ◽  
Rank Correlation ◽  
Hypoxic Condition ◽  
Underlying Mechanism ◽  
Beclin 1 ◽  
Endometrial Stromal Cells ◽  
Tnf Α ◽  
Ectopic Endometrium

AimHigh mobility group box (HMGB)-1 has been implicated in endometriosis due to the important regulatory roles of inflammation in endometriosis. The aim of the present study was to explore the roles of HMGB-1 in endometriosis and to elucidate the underlying mechanism.MethodsEndometrial specimens were collected from women with endometriosis and healthy volunteers. Immunohistochemistry staining was used to determine the expression patterns and localization of HMGB-1 in the normal, eutopic and ectopic endometrial tissues. Western blotting and qRT-PCR were used to determine the mRNA and protein levels of inflammatory cytokines [interleukin (IL)-6, tumor necrosis factor (TNF)-α and IL-1β], autophagy-related markers [beclin-1, autophagy-related (atg)13, microtubule-associated protein light chain (LC)3-I, LC-II and p62] and HMGB-1, respectively. Spearman’s rank correlation analysis was employed to investigate the correlation between HMGB-1 with inflammatory cytokines and beclin-1. Besides, human endometrial stromal cells (HESCs) were isolated from ectopic endometrium and subsequently transfected with shRNA against HMGB-1. After the transfected cells were subjected to hypoxia, ELISA was used to determine the levels of HMGB-1 and inflammatory cytokines in the cell supernatant. Western blotting was used to determine the expression levels of autophagy-related markers in the cells.ResultsPositive correlations were observed between HMGB-1 and the inflammatory cytokines. In addition, a positive correlation was also identified between HMGB-1 and beclin-1 in the ectopic endometrium. Further results demonstrated that autophagy-related markers beclin-1, atg13 and p62 were significantly upregulated in the ectopic endometrium. In addition, HMGB-1 knockdown suppressed the levels of inflammatory cytokines IL-6, TNF-α and IL-1β and autophagy-related markers beclin-1 and atg13, while upregulated p62 in HESCs under hypoxic condition.ConclusionKnockdown of HMGB-1 under hypoxic condition regulated inflammatory cytokines and autophagy-related markers. HMGB-1 might contribute to the development of endometriosis in part through regulating inflammatory response and autophagy.

scholarly journals An Evidence for a Novel Antiviral Mechanism of Teleost Fish: Serum-Derived Exosomes Inhibit Virus Replication Through Incorporating Mx1 Protein

2021 ◽  
Author(s):  
Changjun Guo ◽  
Jian He ◽  
Zhi-Min Li ◽  
Yuanyuan Wang ◽  
Chen nan nan ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Teleost Fish ◽  
Protein Composition ◽  
Underlying Mechanism ◽  
Antiviral Effect ◽  
Mandarin Fish ◽  
Underlying Mechanisms ◽  
Antiviral Mechanism ◽  
Fish Serum

Exosomes are associated with cancer progression, pregnancy, cardiovascular diseases, central nervous system–related diseases, immune responses and viral pathogenicity. However, study on the role of exosomes in the immune response of teleost fish, especially antiviral immunity, is limited. Herein, serum-derived exosomes from mandarin fish were used to investigate antiviral effect for the exosomes of teleost fish. Exosomes were isolated from mandarin fish serum by ultracentrifugation could internalize into Mandarin fish fry (MFF-1) cells and inhibited Infectious spleen and kidney necrosis virus (ISKNV) infection. To further investigated the underlying mechanisms of exosomes in inhibiting ISKNV infection. The protein composition of serum-derived exosomes was by analysis mass spectrometry and found that myxovirus resistance 1 (Mx1) was incorporated in the exosomes. Furthermore, the scMx1 protein was proved transferred to the recipient cells though the exosomes. Our results found that the serum-derived exosomes from mandarin fish could inhibit ISKNV replication and suggested an underlying mechanism of the serum-derived exosomes antivirus is that serum-derived exosomes incorporation of the Mx1 protein into exosomes and delivery into recipient cells. This study provided an evidence for the important antiviral role of exosomes in the immune system of teleost fish.

scholarly journals Structures of an engineered phospholipase D with specificity for secondary alcohol transphosphatidylation: Insights into plasticity of substrate binding and activation

2021 ◽  
Author(s):  
Ariela Samantha ◽  
Jasmina Damnjanović ◽  
Yugo Iwasaki ◽  
Hideo Nakano ◽  
Alice Vrielink
Keyword(s):  
Phospholipase D ◽  
Catalytic Mechanism ◽  
Inositol Phosphate ◽  
Substrate Binding ◽  
Secondary Alcohol ◽  
Molecular Size ◽  
Underlying Mechanism ◽  
Head Group ◽  
Wild Type ◽  
Primary Alcohols

Phospholipase D (PLD) is an enzyme useful for the enzymatic modification of phospholipids.  In the presence of primary alcohols, the enzyme catalyses transphosphatidylation of the head group of phospholipid substrates to synthesize a modified phospholipid product.  However, the enzyme is specific for primary alcohols and thus the limitation of the molecular size of the acceptor compounds has restricted the type of phospholipid species that can be synthesised.  An engineered variant of PLD from Streptomycesantibioticus termed TNYR SaPLD was developed capable of synthesizing 1-phosphatidylinositol with positional specificity of up to 98%. To gain a better understanding of the substrate binding features of the TNYR SaPLD, crystal structures have been determined for the free enzyme and its complexes with phosphate, phosphatidic acid and 1-inositol phosphate.  Comparisons of these structures with the wild-type SaPLD show a larger binding site able to accommodate a bulkier secondary alcohol substrate as well as changes to the position of a flexible surface loop proposed to be involved in substrate recognition.  The complex of the active TNYR SaPLD with 1-inositol phosphate reveals a covalent intermediate adduct with the ligand bound to H442 rather than to H168, the proposed nucleophile in the wild type enzyme.  This structural feature suggests that the enzyme exhibits plasticity of the catalytic mechanism different from what has been reported to date for PLDs.  These structural studies provide insights into the underlying mechanism that governs the recognition of myo-inositol by TNYR SaPLD, and an important foundation for further studies of the catalytic mechanism.

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