scholarly journals MicroRNA-155 Promotes Atherosclerosis Inflammation via Targeting SOCS1

2015 ◽  
Vol 36 (4) ◽  
pp. 1371-1381 ◽  
Author(s):  
Yang Yang ◽  
Lixia Yang ◽  
Xing Liang ◽  
Guofu Zhu
Keyword(s):  
Functional Role ◽  
Inflammatory Cytokine ◽  
Activity Levels ◽  
Chemokine Production ◽  
Arterial Walls ◽  
Atherosclerosis Progression ◽  
Pathophysiological Process ◽  
Expression And Activity

Aims: Accumulating evidence suggests that atherosclerotic progression depends on persistent and chronic inflammation in the arterial walls. MicroRNA-155 is reportedly involved in cardiovascular disease and has been implicated as a pro-inflammation regulator. Although some researchers have focused on microRNA-155 as an atherosclerosis regulator, the mechanisms by which microRNA-155 functions as a putative pro-atherosclerosis microRNA are largely unknown. This study aims to analyze microRNA-155's effects on atherosclerotic inflammation and to explore its mechanism. Methods: MicroRNA-155's effects on atherosclerotic inflammation were observed along with the expression and activity levels of SOCS1, STAT3 and NF-κB though microRNA-155 inhibition or overexpression. Results: Highly expressions of microRNA-155 in oxLDL-stimulated macrophages and atherosclerosis mice were inversely correlated with SOCS1 expression. Ectopic microRNA-155 overexpression significantly promoted inflammatory cytokine and chemokine production and atherosclerosis progression. We then observed microRNA-155's functional role in the atherosclerotic pathophysiological process in vivo and in vitro. The observation revealed that by enhancing STAT3 and NF-κB signaling and facilitating immune inflammation by targeting SOCS1, microRNA-155 plays a promotable role in atherosclerosis progression. Conclusions: microRNA-155 works as a promoter in the atherosclerotic procession. Its mechanism may include enhancing inflammatory response in atherosclerosis by increasing STAT3 and NF-κB signaling via targeting SOCS1.

scholarly journals Bone marrow mesenchymal stem cells promote prostate cancer cell stemness via cell–cell contact to activate the Jagged1/Notch1 pathway

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ji-wen Cheng ◽  
Li-xia Duan ◽  
Yang Yu ◽  
Pu Wang ◽  
Jia-le Feng ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Western Blot ◽  
Cell Contact ◽  
Activity Levels ◽  
Tumor Resistance ◽  
Cell Cell

Abstract Background Mesenchymal stem cells (MSCs) play a crucial role in cancer development and tumor resistance to therapy in prostate cancer, but the influence of MSCs on the stemness potential of PCa cells by cell–cell contact remains unclear. In this study, we investigated the effect of direct contact of PCa cells with MSCs on the stemness of PCa and its mechanisms. Methods First, the flow cytometry, colony formation, and sphere formation were performed to determine the stemness of PCaMSCs, and the expression of stemness-related molecules (Sox2, Oct4, and Nanog) was investigated by western blot analysis. Then, we used western blot and qPCR to determine the activity levels of two candidate pathways and their downstream stemness-associated pathway. Finally, we verified the role of the significantly changed pathway by assessing the key factors in this pathway via in vitro and in vivo experiments. Results We established that MSCs promoted the stemness of PCa cells by cell–cell contact. We here established that the enhanced stemness of PCaMSCs was independent of the CCL5/CCR5 pathway. We also found that PCaMSCs up-regulated the expression of Notch signaling-related genes, and inhibition of Jagged1-Notch1 signaling in PCaMSCs cells significantly inhibited MSCs-induced stemness and tumorigenesis in vitro and in vivo. Conclusions Our results reveal a novel interaction between MSCs and PCa cells in promoting tumorigenesis through activation of the Jagged1/Notch1 pathway, providing a new therapeutic target for the treatment of PCa.

Azithromycin suppresses P. gingivalis LPS-induced pro-inflammatory cytokine and chemokine production by human gingival fibroblasts in vitro

2014 ◽  
Vol 19 (2) ◽  
pp. 221-227 ◽  
Author(s):  
C. J. Doyle ◽  
T. R. Fitzsimmons ◽  
C. Marchant ◽  
A. A. S. S. K. Dharmapatni ◽  
R. Hirsch ◽  
...  
Keyword(s):  
Inflammatory Cytokine ◽  
Human Gingival Fibroblasts ◽  
Gingival Fibroblasts ◽  
Chemokine Production

scholarly journals WNT-5A regulates TGF-β-related activities in liver fibrosis

2017 ◽  
Vol 312 (3) ◽  
pp. G219-G227 ◽  
Author(s):  
Leonie Beljaars ◽  
Sara Daliri ◽  
Christa Dijkhuizen ◽  
Klaas Poelstra ◽  
Reinoud Gosens
Keyword(s):  
Liver Fibrosis ◽  
Functional Role ◽  
Collagen Type ◽  
Collagen Type I ◽  
Matrix Proteins ◽  
Type I ◽  
Human Livers

WNT-5A is a secreted growth factor that belongs to the noncanonical members of the Wingless-related MMTV-integration family. Previous studies pointed to a connection between WNT-5A and the fibrogenic factor TGF-β warranting further studies into the functional role of WNT-5A in liver fibrosis. Therefore, we studied WNT-5A expressions in mouse and human fibrotic livers and examined the relation between WNT-5A and various fibrosis-associated growth factors, cytokines, and extracellular matrix proteins. WNT-5A gene and protein expressions were significantly increased in fibrotic mouse and human livers compared with healthy livers. Regression or therapeutic intervention in mice resulted in decreased hepatic WNT-5A levels paralleled by lower collagen levels. Immunohistochemical analysis showed WNT-5A staining in fibrotic septa colocalizing with desmin staining indicating WNT-5A expression in myofibroblasts. In vitro studies confirmed WNT-5A expression in this cell type and showed that TGF-β significantly enhanced WNT-5A expression in contrast to PDGF-BB and proinflammatory cytokines IL-1β and TNF-α. Additionally, TGF-β induces the expression of the WNT receptors FZD2 and FZD8. After silencing of WNT-5A, reduced levels of collagen type I, vimentin, and fibronectin in TGF-β-stimulated myofibroblasts were measured compared with nonsilencing siRNA-treated controls. Interestingly, the antifibrotic cytokine IFNγ suppressed WNT-5A in vitro and in vivo. IFNγ-treated fibrotic mice showed significantly less WNT-5A expression compared with untreated fibrotic mice. In conclusion, WNT-5A paralleled collagen I levels in fibrotic mouse and human livers. WNT-5A expression in myofibroblasts is induced by the profibrotic factor TGF-β and plays an important role in TGF-β-induced regulation of fibrotic matrix proteins, whereas its expression can be reversed upon treatment, both in vitro and in vivo. NEW & NOTEWORTHY This study describes the localization and functional role of WNT-5A in human and mouse fibrotic livers. Hepatic WNT-5A expression parallels collagen type I expression. In vivo and in vitro, the myofibroblasts were identified as the key hepatic cells producing WNT-5A. WNT-5A is under control of TGF-β and its activities are primarily profibrotic.

Expression and activity of thrombomodulin in human gingival epithelium: in vivo and in vitro studies

2000 ◽  
Vol 35 (3) ◽  
pp. 146-157 ◽  
Author(s):  
T. Matsuyama ◽  
Y. Izumi ◽  
K. Shibatate ◽  
Y. Yotsumoto ◽  
H. Obama ◽  
...  
Keyword(s):  
In Vitro Studies ◽  
Gingival Epithelium ◽  
Expression And Activity

In vivo and in vitro effects of fluoroquinolones on lipopolysaccharide-induced pro-inflammatory cytokine production

2009 ◽  
Vol 15 (3) ◽  
pp. 168-173 ◽  
Author(s):  
Hiromi Ogino ◽  
Miho Fujii ◽  
Mariko Ono ◽  
Kayoko Maezawa ◽  
Junko Kizu ◽  
...  
Keyword(s):  
Inflammatory Cytokine ◽  
Cytokine Production ◽  
Inflammatory Cytokine Production ◽  
In Vitro Effects

scholarly journals Induction of Host Chemotactic Response by Encephalitozoon spp.

2006 ◽  
Vol 75 (4) ◽  
pp. 1619-1625 ◽  
Author(s):  
Jeffrey Fischer ◽  
Jeffrey West ◽  
Nnenaya Agochukwu ◽  
Colby Suire ◽  
Hollie Hale-Donze
Keyword(s):  
Inflammatory Responses ◽  
Kinetic Studies ◽  
Protein Profiling ◽  
Diagnostic Tools ◽  
Emerging Pathogens ◽  
Chemokine Production ◽  
Human Macrophages ◽  
Monocyte Migration

ABSTRACT Microsporidians are a group of emerging pathogens typically associated with chronic diarrhea in immunocompromised individuals. The number of reports of infections with these organisms and the disseminated pathology is growing as diagnostic tools become more readily available. However, little is known about the innate immune response induced by and generated against these parasites. Using a coculture chemotaxis system, primary human macrophages were infected with Encephalitozoon cuniculi or Encephalitozoon intestinalis, and the recruitment of naïve monocytes was monitored. Encephalitozoon spp. induced an average threefold increase in migration of naïve cells 48 h postinfection, which corresponded to optimal infection of monocyte-derived-macrophages. A limited microarray analysis of infected macrophages revealed several chemokines involved in the inflammatory responses whose expression was upregulated, including CCL1, CCL2, CCL3, CCL4, CCL7, CCL15, CCL20, CXCL1, CXCL2, CXCL3, CXCL5, and CXCL8. The levels of 6 of 11 chemokines also present in the microarray were confirmed to be elevated by protein profiling. Kinetic studies confirmed that secreted CCL2, CCL3, and CCL4 were expressed as early as 6 h postinfection, with peak expression at 12 to 24 h and expression remaining until 48 h postinfection. Neutralization of these chemokines, specifically CCL4, significantly reduced the number of migrating cells in vitro, indicating their role in the induction of monocyte migration. This mechanism of recruitment not only supports the evidence that in vivo cellular infiltration occurs but also provides new hosts for the parasites, which escape macrophages by rupturing the host cell. To our knowledge, this is the first documentation that chemokine production is induced by microsporidian infections in human macrophages.

Abstract 3: Apolipoprotein A-I Inhibits Streptococcal Cell Wall-Induced Arthritis in the Rat in an ABCA1-dependent Manner

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Ben J Wu ◽  
Kwok L Ong ◽  
Sudichhya Shrestha ◽  
Kang Chen ◽  
Philip J Barter ◽  
...  
Keyword(s):  
Cell Wall ◽  
Inflammatory Cytokine ◽  
Density Lipoprotein ◽  
Joint Inflammation ◽  
Chronic Inflammatory Disease ◽  
Dependent Manner ◽  
Tlr2 Expression ◽  
Streptococcal Cell Wall

Introduction. Arthritis is a chronic inflammatory disease characterized by joint inflammation and destruction, reduced high-density lipoprotein (HDL) levels, and increased cardiovascular risk. Objective To determine if apolipoprotein (apo) A-I, the main HDL apolipoprotein, prevents joint inflammation in arthritis. Methods and Results In vivo: Arthritis was induced in female Lewis rats with a single 15 mg/kg intraperitoneal streptococcal cell wall peptidoglycan-polysaccharide (PG-PS) injection and quantified as a combined forepaw and hindpaw inflammation score. Arthritis progressed from an initial, acute phase of joint inflammation during the first 4 days post-PG-PS administration to remission by day 8, followed by chronic joint inflammation up to sacrifice at day 21. Two intravenous infusions of lipid-free apoA-I (8 mg/kg) 24 h pre- and 24 h post-PG-PS injection reduced the acute and chronic joint inflammation by 63±9% at day 3 and by 61±8% at day 21. Infusion of apoA-I at days 7, 9 and 11 post-PG-PS injection reduced the chronic response by 43±11% at day 21. ApoA-I infusions at 24 h prior to and at days 1, 7, 9, 11 post-PG-PS injection reduced joint inflammation by 61±5% at day 3 and by 90±5% at day 21 (p<0.05 for all vs saline infusion). These beneficial effects of apoA-I were accompanied by a reduced inflammatory white blood cell count, reduced pro-inflammatory cytokine levels in synovial fluid, and reduced macrophage accumulation, toll-like receptor 2 (TLR2) and inflammatory cytokine expression in synovial tissue. In vitro: Human monocyte-derived macrophages (HMDMs) were pre-incubated with lipid-free apoA-I, then stimulated with PG-PS (20 μg/mL). Pre-incubation with apoA-I inhibited PG-PS-induced TLR2 and MyD88, a TLR2 adapter protein, expression. Nuclear factor-κB activation and pro-inflammatory cytokine production were also attenuated. These anti-inflammatory effects of apoA-I were abolished in HMDMs transfected with ATP-binding cassette transporter 1 (ABCA1) siRNA. Conclusions These findings establish that apoA-I attenuates PG-PS induced arthritis in the rat. These effects may involve ABCA-1 and inhibition of TLR2 expression and activation.

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