scholarly journals The Role of IL-6RA in UHMWPE Promotes Proliferation in Fibro-Like Synovial Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-9
Author(s):  
Xianlun Pang ◽  
Jiang Yang ◽  
Xiaoli Zhen ◽  
Hai Nie ◽  
Hao Qin ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Immunofluorescent Staining ◽  
Inflammatory Factors ◽  
Synovial Cells ◽  
Interleukin 6 Receptor ◽  
Apoptosis And Inflammation ◽  
Related Proteins ◽  
The Relationship ◽  
Surrounding Bone

UHMWPE granule could induce macrophages and inflammatory responses in interfacial tissues, which eliminated the wear debris of UHMWPE component and further induced dissolution of the surrounding bone, leading aseptic loosening. However, the mechanism of synovial cells, especially fibroblast-like synovial (FLS) cells response to UHMWPE, remains unknown. Herein we choose FLS cells as research object. Vimentin (+) CD68 (-) was identified by flow cytometry and immunofluorescent staining assay, and the cells were identified as FLS cells, which was consistent with the experimental requirements. The inhibitory evaluation showed that UHMWPE could significantly promote the proliferation and inhibit apoptosis of FLS cells in dose- and time-dependent manners and increase the levels of proinflammatory cytokines, including IL-6, IL-1β, TNF-α, PGE2, MMP2, and LOX. UHMWPE also can induce the expression of mIL-6R protein in FLS cells and further investigate the relationship between apoptosis and inflammation. Interestingly enough, when we added the interleukin-6 receptor antagonist (IL-6RA), the expression levels of proapoptosis-related proteins increased; in other words, UHMWPE-induced antiapoptosis diminished by IL-6RA (50 μg/ml). Taken together, these findings clearly demonstrated that UHMWPE promote growth in FLS cells through upregulating inflammatory factors to produce antiapoptotic effect.

scholarly journals Lipopolysaccharides promote pulmonary fibrosis in silicosis through the aggravation of apoptosis and inflammation in alveolar macrophages

2020 ◽  
Vol 15 (1) ◽  
pp. 598-605
Author(s):  
Shiyi Tan ◽  
Shang Yang ◽  
Mingke Chen ◽  
Yurun Wang ◽  
Li Zhu ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Alveolar Macrophages ◽  
Inflammatory Factors ◽  
Necrosis Factor Alpha ◽  
Defensive Role ◽  
Factor Alpha ◽  
Apoptosis And Inflammation ◽  
The Relationship ◽  
Lps Treatment ◽  
Necrosis Factor

AbstractAlveolar macrophages (AMs) play an important defensive role by removing dust and bacteria from alveoli. Apoptosis of AMs is associated with lung fibrosis; however, the relationship between this apoptotic event and environmental factors, such as the presence of lipopolysaccharides (LPSs) in the workplace, has not yet been addressed. To investigate whether exposure to LPS can exacerbate fibrosis, we collected AMs from 12 male workers exposed to silica and incubated them in the presence and absence of LPS for 24 h. We show that the levels of cleaved caspase-3 and pro-inflammatory cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha were increased in these AMs following LPS treatment. Moreover, we demonstrate that LPS exposure aggravated apoptosis and the release of inflammatory factors in AMs in a mouse model of silicosis, which eventually promoted pulmonary fibrosis. These results suggest that exposure to LPS may accelerate the progression of pulmonary fibrosis in silicosis by increasing apoptosis and inflammation in AMs.

scholarly journals The Inflammatory Role of Pro-Resolving Mediators in Endometriosis: An Integrative Review

2021 ◽  
Vol 22 (9) ◽  
pp. 4370
Author(s):  
Cássia de Fáveri ◽  
Paula M. Poeta Fermino ◽  
Anna P. Piovezan ◽  
Lia K. Volpato
Keyword(s):  
Intracellular Signaling ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Critical Role ◽  
Integrative Review ◽  
Inflammatory Factors ◽  
Resolvin D1 ◽  
Endogenous Factors

The pathogenesis of endometriosis is still controversial, although it is known that the inflammatory immune response plays a critical role in this process. The resolution of inflammation is an active process where the activation of endogenous factors allows the host tissue to maintain homeostasis. The mechanisms by which pro-resolving mediators (PRM) act in endometriosis are still little explored. Thus, this integrative review aims to synthesize the available content regarding the role of PRM in endometriosis. Experimental and in vitro studies with Lipoxin A4 demonstrate a potential inhibitory effect on endometrial lesions’ progression, attenuating pro-inflammatory and angiogenic signals, inhibiting proliferative and invasive action suppressing intracellular signaling induced by cytokines and estradiol, mainly through the FPR2/ALX. Investigations with Resolvin D1 demonstrated the inhibition of endometrial lesions and decreased pro-inflammatory factors. Annexin A1 is expressed in the endometrium and is specifically present in women with endometriosis, although the available studies are still inconsistent. Thus, we believe there is a gap in knowledge regarding the PRM pathways in patients with endometriosis. It is important to note that these substances’ therapeutic potential is evident since the immune and abnormal inflammatory responses play an essential role in endometriosis development and progression.

Abstract WMP31: Dedifferentiation of Smooth Muscle Cells and its Potential Contribution to Pathogenesis of Intracranial Aneurysms

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Mieko Oka ◽  
Nobuhiko Ohno ◽  
Takakazu Kawamata ◽  
Tomohiro Aoki
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Inflammatory Responses ◽  
Muscle Cells ◽  
Inflammatory Factors ◽  
Potential Contribution ◽  
Electron Microscopic

Introduction: Intracranial aneurysm (IA) affects 1 to 5 % in general public and becomes the primary cause of subarachnoid hemorrhage, the most severe form of stroke. However, currently, no drug therapy is available for IAs to prevent progression and rupture of lesions. Elucidation of mechanisms underlying the disease is thus mandatory. Considering the important role of vascular smooth muscle cells (SMCs) in the maintenance of stiffness of arterial walls and also in the pathogenesis of atherosclerosis via mediating inflammatory responses, we in the present study analyzed morphological or phenotypical changes of SMCs during the disease development in the lesions. Methods: We subjected rats to an IA model in which lesions are induced by increase of hemodynamic force loading on intracranial arterial bifurcations and performed histopathological analyses of induced lesions including the electron microscopic examination. We then immunostained specimens from induced lesions to explore factors responsible for dedifferentiation or migration of SMCs. In vitro study was also done to examine effect of some candidate factors on dedifferentiation or migration of cultured SMCs. Results: We first found the accumulation of SMCs underneath the endothelial cell layer mainly at the neck portion of the lesion. These cells was positive for the embryonic form of myosin heavy chain, a marker for the dedifferentiated SMCs, and the expression of pro-inflammatory factors like TNF-α. In immunostaining to explore the potential factor regulating the dedifferentiation of SMCs, we found that Platelet-derived growth factor-BB (PDGF-BB) was expressed in endothelial cells at the neck portion of IA walls. Consistently, recombinant PDGF-BB could promote the dedifferentiate of SMCs and chemo-attracted them in in vitro. Finally, in the stenosis model of the carotid artery, PDGF-BB expression was induced in endothelial cells in which high wall shear stress was loaded and the dedifferentiation of SMCs occurred there. Conclusions: The findings from the present study imply the role of dedifferentiated SMCs partially recruited by PDGF-BB from endothelial cells in the formation of inflammatory microenvironment at the neck portion of IA walls, leading to the progression of the disease.

Abstract TP99: Human Lung Endothelial Cell Anti-Inflammatory and Regenerative Responses in Acute Ischemic Stroke

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Nikunj Satani ◽  
Kaavya Giridhar ◽  
Natalia Wewior ◽  
Dominique D Norris ◽  
Scott D Olson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Inflammatory Responses ◽  
Inflammatory Factors ◽  
Stroke Severity ◽  
Stroke Patients ◽  
Anti Inflammatory ◽  
Lung Endothelial Cells ◽  
Stroke Mimic

Background: Inflammatory responses after stroke consists of central and peripheral immune responses. The role of the spleen after stroke is well-known, however the role of the lungs has not been studied in detail. We explored the relation between stroke severity and immunomodulatory changes in lung endothelial cells. Methods: Human pulmonary endothelial cells (hPECs, Cell Biologics) were cultured at passage 3. Serum from stroke patients with NIH Stroke Scale (NIHSS) severity ranging from 0 to 20 was collected at 24 hours after stroke. hPECs were exposed to media with 1) 10% FBS alone (N=6), 2) 10% serum from stroke patients (N=72), or 3) 10% serum from stroke mimic patients (N=6). After 3 hour of exposure, fresh media was added and secretomes from hPECs were measured after 24 hours. We isolated RNA from hPECs after 3 hour of serum exposure and measured gene expression (N=6 for each group). Secretome and gene changes in hPECs were analyzed based on stroke severity, tPA treatment, and co-morbidities. Results: Serum from stroke patients reduced the secretion of IL-8, MCP-1 and Fractalkine (p<0.01), and increased the secretion of VEGF and BDNF (p<0.01) from hPECs. These effects were more pronounced depending on stroke severity (Fig). There was no effect of tPA or T2DM on hPECs secretomes. There was significantly reduced gene expression of IL-6, IL-8, MCP-1 and IL-1β and significantly higher expression of ICAM1, IGF-1 and TGF-β1 as compared to stroke mimics. Conclusion: Exposure of hPECs to serum from stroke patients alters their immunomodulatory properties. Higher severity of stroke leads to more protective response from hPECs by reducing the secretion of pro-inflammatory factors, while increasing the secretion of anti-inflammatory factors.

scholarly journals MR Assessment of Acute Pathologic Process after Myocardial Infarction in a Permanent Ligation Mouse Model: Role of Magnetic Nanoparticle-Contrasted MRI

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Cheongsoo Park ◽  
Eun-Hye Park ◽  
Jongeun Kang ◽  
Javeria Zaheer ◽  
Hee Gu Lee ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Mouse Model ◽  
Magnetic Nanoparticle ◽  
Inflammatory Responses ◽  
Myocardial Infarct ◽  
Correlation Coefficients ◽  
Myocardial Infarct Size ◽  
Manganese Enhanced Mri ◽  
The Relationship

We evaluated the relationship between myocardial infarct size and inflammatory response using cardiac magnetic resonance imaging (CMR) in an acute myocardial infarction (AMI) mouse model. Myocardial infarction (MI) was induced in 14 mice by permanent ligation of the left anterior descending artery. Late gadolinium enhancement (LGE), manganese-enhanced MRI (MEMRI), and magnetofluorescent nanoparticle MRI (MNP-MRI) were performed 1, 2, and 3 days after MI, respectively. The size of the enhanced lesion was quantitatively determined using Otsu’s thresholding method in area-based and sector-based approaches and was compared statistically. Linear correlation between the enhanced lesion sizes was evaluated by Pearson’s correlation coefficients. Differences were compared using Bland-Altman analysis. The size of the inflammatory area determined by MNP-MRI (57.1 ± 10.1%) was significantly larger than that of the infarct area measured by LGE (40.8 ± 11.7%, P<0.0001) and MEMRI (44.1 ± 14.9%, P<0.0001). There were significant correlations between the sizes of the infarct and inflammatory lesions (MNP-MRI versus LGE: r=0.3418, P=0.0099; MNP-MRI versus MEMRI: r=0.4764, P=0.0002). MNP-MRI provides information about inflammatory responses in a mouse model of AMI. Thus, MNP-MRI associated with LGE and MEMRI may play an important role in monitoring the disease progression in MI.

scholarly journals RhTrx-1 ameliorates miroglial neuroinflammation after cerebral ischemic stroke

2020 ◽  
Author(s):  
Yang Jiao ◽  
Jianjian Wang ◽  
Huixue Zhang ◽  
Yuze Cao ◽  
Yang Qu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Inflammatory Response ◽  
Inflammatory Responses ◽  
Inflammatory Factors ◽  
Experimental Stroke ◽  
Inflammasome Activation ◽  
Cerebral Ischemic

Abstract Background Microglia are rapidly activated after ischemic stroke and participate in the occurrence of neuroinflammation, which exacerbates the injury of ischemic stroke. Receptor Interacting Serine Threonine Kinase 1 (RIPK1) is thought to be involved in the development of inflammatory responses, but its role in ischemic microglia remains unclear. Here, we applied recombinant human thioredoxin-1 (rhTrx-1), a potential neuroprotective agent, to explore the role of rhTrx-1 in inhibiting RIPK1-mediated neuroinflammatory responses in microglia. Method Middle cerebral artery occlusion (MCAO) and Oxygen and glucose deprivation (OGD) were conducted for in vivo and in vitro experimental stroke models. The expression of RIPK1 in microglia after ischemia was examined. The inflammatory response of microglia was analyzed after treatment with rhTrx-1 and Necrostatin-1 (Nec-1, inhibitors of RIPK1), and the mechanisms were explored. In addition, the effects of rhTrx-1 on neurobehavioral deficits and cerebral infarct volume were examined. Results RIPK1 expression was detected in microglia after ischemia. Molecular docking results showed that rhTrx-1 could directly bind to RIPK1. In vitro experiments found that rhTrx-1 reduced necroptosis, mitochondrial membrane potential damage, Reactive oxygen species (ROS) accumulation and NLR Family, pyrin domain-containing 3 protein (NLRP3) inflammasome activation by inhibiting RIPK-1 expression, and regulated microglial M1/M2 phenotypic changes, thereby reducing the release of inflammatory factors. Consistently, in vivo experiments found that rhTrx-1 treatment attenuated cerebral ischemic injury by inhibiting the inflammatory response. Conclusion Our study demonstrates the role of RIPK1 in microglia-arranged neuroinflammation after cerebral ischemia. Administration of rhTrx-1 provides neuroprotection in ischemic stroke-induced microglial neuroinflammation by inhibiting RIPK1 expression.

scholarly journals THE ROLE OF INTRATUMORAL DENDRITIC CELLS IN THE PROGRESSION OF SQUAMOUS CELL CARCINOMAS

2019 ◽  
Vol 18 (4) ◽  
pp. 50-58
Author(s):  
L. N. Bondar ◽  
L. A. Tashireva ◽  
O. V. Savenkova ◽  
E. L. Choynzonov ◽  
V. M. Perelmuter
Keyword(s):  
Overall Survival ◽  
Squamous Cell ◽  
Inflammatory Responses ◽  
Survival Rates ◽  
Metastatic Tumor ◽  
Squamous Cell Carcinomas ◽  
The Relationship ◽  
Disease Free ◽  
Overall Survival Rates

The aim of the studywas to summarize data on the role of tumor-associated dendritic cells (DC) in the formation of squamous cell carcinoma microenvironment, their participation in the development of immune inflammatory responses in the tumor stroma and relation to tumor progression.Material and Methods. We analyzed 79 publications available from Pubmed, Google Scholar, Elibrary databases from January 2000 to December 2017.Results. The characteristics of different types of DC, including Langerhans cells (CR), were presented. The different methods of DC identification were described. The information on the presence of DC in squamous cell carcinomas was analyzed. The influence of the tumor on DCs, as well as the relationship between the number and functional characteristics of DCs and invasive/metastatic tumor potentialities was described. The prognostic value of DCs and their effect on disease-free, metastasis-free and overall survival rates were analyzed. The data on the association between DCs and the response to chemoradiotherapy were presented. The analysis of the relationship between the DC characteristics and the development of immuno-inflammatory responses in the tumor microenvironment was carried out.Conclusion. The methodological approaches to the detection of DCs are variable, but the sensitivity of each method, as well as the comparison of different methods for estimating the number and functional characteristics of DCs, have been little studied. There is no data on the relationship between the length of DC dendrites and the parameters of invasive/metastatic tumor potentialities, disease-free, metastasis-free and overall survival rates. Numerous studies indicate the association between the number of DCs and the tumor progression, however these data are contradictory. There is no data about the relationship between the number of DCs and hematogenous metastasis of squamous cell carcinomas. The association of tumor-associated DC with the types of immunoinflammatory responses in the tumor microenvironment has been insufficiently studied. 

MIR-141 is Negatively Correlated With TLR4 in Neonatal Sepsis and Regulates LPS-induced Inflammatory Responses in Monocytes

2020 ◽  
Author(s):  
Xinyu Lin ◽  
Yaohui Wang
Keyword(s):  
Roc Curve ◽  
Neonatal Sepsis ◽  
Inflammatory Responses ◽  
Neonatal Morbidity ◽  
Diagnostic Value ◽  
Inflammatory Factors ◽  
Diagnostic Biomarker ◽  
Qrt Pcr ◽  
And Control ◽  
The Relationship

Abstract Background: Neonatal sepsis is an inflammatory system syndrome caused by bacteria or viruses, which is the main cause of neonatal morbidity and mortality. But currently there is a lack of an ideal biomarker to meet the standard. The abnormally expression of miRNAs may be a group of potential diagnostic biomarkers in neonatal sepsis.Methods: First, qRT-PCR was used to calculate the expression of miR-141 in the serum of neonatal with sepsis and control. The diagnostic value of PCT and serum miR-141 was evaluated by receiver operating characteristic (ROC) curve. Second, the relationship between miR-141 and TLR4 was verified using luciferase report assay. An inflammation model was established using monocytes with the LPS treatment. Elisa analyzed the relationship between miR-141 and inflammatory factors.Results: qRT-PCR found that the expression of miR-141 in neonatal sepsis was significantly lower than healthy controls. ROC curve shows that miR-141 has high diagnostic accuracy. LPS stimulation in monocytes also led to a decrease in the expression of miR-141. Luciferase report assay proves that miR-141 can target and regulate TLR4 expression. ELISA proved that overexpression of miR-141 has the effect of inhibiting the LPS-induced inflammation in monocytes.Conclusion: In conclusion, miR-141 serves as a candidate diagnostic biomarker and is involved in the regulation of inflammatory response in the development of neonatal sepsis. Overexpression of miR-141 inhibits LPS-induced inflammation by targeting TLR4. Therefore, miR-141 is expected to be a potential diagnostic biomarker and a therapeutic target in neonatal sepsis.

Critical role of microglia in the inflammatory response after spinal injury

2015 ◽  
Vol 3 (3) ◽  
pp. 453-462
Author(s):  
Ya-Yun Shi
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Responses ◽  
Spinal Injury ◽  
Critical Role ◽  
Cell Types ◽  
Inflammatory Factors ◽  
Cytokines And Chemokines ◽  
Cord Injury

Spinal cord injury induces a robust neuroinflammatory response that includes marked changes in the variety of endogenous CNS cell types specially microglia. In response to spinal injury, microglia undergo dramatic changes in cell morphology and promote inflammatory responses, which result in production of inflammatory factors and oxidative stress including reactive oxygen species. Further pro-inflammatory cytokines and chemokines are also rapidly up-regulated and likely contribute to microglial activation. This topic review will explore the current research on microglial responses to spinal injury and the recent progress in the pharmacologic and molecular targeting of microglia in spinal injury. Finally, we explore the argument for a positive versus negative role of microglia after spinal cord injury.

scholarly journals The role of activating transcription factor 6 in hydroxycamptothecin-induced fibroblast autophagy and apoptosis

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Jin Tao ◽  
Hui Chen ◽  
Xiaolei Li ◽  
Jingcheng Wang
Keyword(s):  
Transcription Factor ◽  
Western Blot ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Cell Counting ◽  
Immunofluorescent Staining ◽  
Fibroblast Proliferation ◽  
Activating Transcription Factor ◽  
Related Proteins

Abstract Background The over-proliferation of fibroblasts is considered to be the main cause of scar adhesion after joint surgery. Hydroxycamptothecin (HCPT), though as a potent antineoplastic drug, shows preventive effects on scar adhesion. This study aimed to investigate the role of activating transcription factor 6 (ATF-6) in the HCPT-induced inhibition of fibroblast viability. Methods The cell counting kit-8 (CCK-8) assay, western blot analysis, lentivirus-mediated gene silencing, transmission electron microscopy (TEM) analysis, immunofluorescent staining for autophagy-related protein light chain 3 (LC3) were used to explore the effect of HCPT on triggering fibroblast apoptosis and inhibiting fibroblast proliferation, and the involvement of possible signaling pathways. Results It was found that HCPT exacerbated fibroblast apoptosis and repressed its proliferation. Subsequently, endoplasmic reticulum stress (ERS)-related proteins were determined by western blot prior to ATF6 p50 was screened out and reexamined after it was silenced. As a result, ATF6-mediated ERS played a role in HCPT-induced fibroblast apoptosis. Autophagy-related proteins and autophagosomes were detected after the HCPT administration using western blot and TEM analyses, respectively. Autophagy was activated after the HCPT treatment. With the co-treatment of autophagy inhibitor 3-methyladenine (3-MA), both the western blot analysis and the CCK-8 assay showed inhibited autophagy, which indicated that the effect of HCPT on fibroblast proliferation was partially reversed. Besides, the LC3 immunofluorescence staining revealed suppressed autophagy after silencing ATF6 p50. Conclusion Our results demonstrate that HCPT acts as a facilitator of fibroblast apoptosis and inhibitor of fibroblast proliferation for curbing the postoperative scar adhesion, in which the ATF6-mediated ERS pathway and autophagy are involved.

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