scholarly journals INHIBITION OF NLRP3 INFLAMMASOME REDUCES APOPTOSIS OF ISLETS AND MIGRATION OF MACROPHAGES AFTER ISLET TRANSPLANTATION

2020 ◽  
Vol 104 (S3) ◽  
pp. S567-S567
Author(s):  
Taisuke Matsuoka ◽  
Gumpei Yoshimatsu ◽  
Tomoko Tanaka ◽  
Ryo Kawakami ◽  
Teppei Yamada ◽  
...  
Keyword(s):  
Islet Transplantation ◽  
Nlrp3 Inflammasome ◽  
And Migration ◽  
Migration Of Macrophages

scholarly journals Salidroside Suppresses the Proliferation and Migration of Human Lung Cancer Cells through AMPK-Dependent NLRP3 Inflammasome Regulation

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Weidong Ma ◽  
Ziyuan Wang ◽  
Yan Zhao ◽  
Qibin Wang ◽  
Yonghong Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Nlrp3 Inflammasome ◽  
Human Lung ◽  
A549 Cells ◽  
Human Lung Cancer ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation ◽  
Human Lung Cancer Cells ◽  
And Migration ◽  
Proliferation And Migration

Inflammatory reactions mediated by the NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome contributes to non-small-cell lung cancer (NSCLC) progression, particularly in patients with bacterial infections. Salidroside (SAL) has recently been shown to suppress lipopolysaccharide- (LPS-) induced NSCLC proliferation and migration, but its mechanism of action remains unclear. It has been shown that SAL improves metabolic inflammation in diabetic rodents through AMP-activated protein kinase- (AMPK-) dependent inhibition of the NLRP3 inflammasome. However, whether the NLRP3 inflammasome is regulated by SAL in NSCLC cells and how its underlying mechanism(s) can be determined require clarification. In this study, human lung alveolar basal carcinoma epithelial (A549) cells were treated with LPS, and the effects of SAL on cell proliferation, migration, AMPK activity, reactive oxygen species (ROS) production, and NLRP3 inflammasome activation were investigated. We found that LPS induction increases the proliferation and migration of A549 cells which was suppressed by SAL. Moreover, SAL protected A549 cells against LPS-induced AMPK inhibition, ROS production, and NLRP3 inflammasome activation. Blocking AMPK using Compound C almost completely suppressed the beneficial effects of SAL. In summary, these results indicate that SAL suppresses the proliferation and migration of human lung cancer cells through AMPK-dependent NLRP3 inflammasome regulation.

scholarly journals Inhibition of NLRP3 inflammasome by MCC950 improves the metabolic outcome of islet transplantation by suppressing IL-1β and islet cellular death

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Taisuke Matsuoka ◽  
Gumpei Yoshimatsu ◽  
Naoaki Sakata ◽  
Ryo Kawakami ◽  
Tomoko Tanaka ◽  
...  
Keyword(s):  
Islet Transplantation ◽  
Nlrp3 Inflammasome ◽  
Specific Inhibitor ◽  
Critical Issue ◽  
Therapeutic Effects ◽  
Survival Ratio ◽  
Cellular Death ◽  
Glucose Levels ◽  
Cytokine Stimulation ◽  
The Impact

Abstract Early rejection is a critical issue to be overcome to achieve successful islet transplantation. NLRP3 inflammasome is a protein complex that mediates the maturation of pro-interleukin (IL)-1β and pro-IL-18 to IL-1β and IL-18, respectively, which induce cellular death. Here, we investigated the impact of NLRP3 inflammasome and the effect of its inhibition by MCC950 in a rodent model of islet transplantation. We assessed the therapeutic effects of MCC950, a specific inhibitor of NLRP3 inflammasome, on gene expression, islet survival ratio and viability, and islet transplantation in mice. NLRP3 inflammasome-related gene (Nlrp3 and Il1b) expression was upregulated in islets stimulated with proinflammatory cytokines and suppressed when incubated with MCC950. Survival ratio and viability of incubated islets were reduced by cytokine stimulation and improved by MCC950. Regarding islet transplantation, the number of apoptotic cells in transplanted islets was reduced by MCC950. Furthermore, the expression of IL-1β in transplanted islets, migration of macrophages around islets, and fluctuation of blood glucose levels were suppressed by MCC950. Our study revealed that NLRP3 inflammasome worsened the therapeutic outcomes of islet transplantation and that MCC950 administration improved glycaemic control in syngeneic mice that underwent islet transplantation by inhibiting inflammation, which suppressed islet death.

scholarly journals Regulation of cellular interactions with laminin by integrin cytoplasmic domains: the A and B structural variants of the alpha 6 beta 1 integrin differentially modulate the adhesive strength, morphology, and migration of macrophages.

1994 ◽  
Vol 5 (6) ◽  
pp. 679-690 ◽  
Author(s):  
L M Shaw ◽  
A M Mercurio
Keyword(s):  
Culture Medium ◽  
Cytoplasmic Domain ◽  
Laminin Receptor ◽  
Cellular Interactions ◽  
Structural Variants ◽  
Cytoplasmic Domains ◽  
Macrophage Cell ◽  
Beta 1 Integrin ◽  
And Migration ◽  
Migration Of Macrophages

Several integrin alpha subunits have structural variants that are identical in their extracellular and transmembrane domains but that differ in their cytoplasmic domains. The functional significance of these variants, however, is unknown. In the present study, we examined the possibility that the A and B variants of the alpha 6 beta 1 integrin laminin receptor differ in function. For this purpose, we expressed the alpha 6A and alpha 6B cDNAs, as well as a truncated alpha 6 cDNA (alpha 6-delta CYT) in which the cytoplasmic domain sequence was deleted after the GFFKR pentapeptide, in P388D1 cells, an alpha 6 deficient macrophage cell line. Populations of stable alpha 6A, alpha 6B, and alpha 6-delta CYT transfectants that expressed equivalent levels of cell surface alpha 6 were obtained by fluorescence-activated cell sorter and shown to form heterodimers with endogenous beta 1 subunits. Upon attachment to laminin, the alpha 6A transfectants extended numerous pseudopodia. In contrast, the alpha 6B transfectants remained rounded and extended few processes. The transfectants were also examined for their ability to migrate toward a laminin substratum using Transwell chambers. The alpha 6A transfectants were three- to fourfold more migratory than the alpha 6B transfectants. The alpha 6-delta CYT transfectants did not attach to laminin in normal culture medium, but they did attach in the presence of Mn2+. The alpha 6-delta CYT transfectants migrated to a lesser extent than either the alpha 6A or alpha 6B transfectants in the presence of Mn2+. The alpha 6 transfectants differed significantly in the concentration of substratum bound laminin required for half-maximal adhesion in the presence of Mn2+:alpha 6A (2.1 micrograms/ml), alpha 6B (6.3 micrograms/ml), and alpha 6-delta CYT (8.8 micrograms/ml). Divalent cation titration studies revealed that these transfectants also differed significantly in both the [Ca2+] and [Mn2+] required to obtain half-maximal adhesion to laminin. These data demonstrate that the A and B variants of the alpha 6 cytoplasmic domain can differentially modulate the function of the alpha 6 beta 1 extracellular domain.

scholarly journals H2-Calponin Regulates Adhesion and Migration of Macrophages

2010 ◽  
Vol 98 (3) ◽  
pp. 728a
Author(s):  
Euy-Myoung Jeong ◽  
J.-P. Jin
Keyword(s):  
And Migration ◽  
Migration Of Macrophages

scholarly journals Activation of NLRP3 inflammasome enhances the proliferation and migration of A549 lung cancer cells

2016 ◽  
Vol 35 (4) ◽  
pp. 2053-2064 ◽  
Author(s):  
YANLI WANG ◽  
HUI KONG ◽  
XIAONING ZENG ◽  
WENRUI LIU ◽  
ZAILIANG WANG ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Nlrp3 Inflammasome ◽  
Lung Cancer Cells ◽  
And Migration ◽  
A549 Lung ◽  
Proliferation And Migration

scholarly journals ROCK1 functions as a suppressor of inflammatory cell migration by regulating PTEN phosphorylation and stability

Blood ◽  
2010 ◽  
Vol 115 (9) ◽  
pp. 1785-1796 ◽  
Author(s):  
Sasidhar Vemula ◽  
Jianjian Shi ◽  
Philip Hanneman ◽  
Lei Wei ◽  
Reuben Kapur
Keyword(s):  
Inflammatory Cells ◽  
Receptor Activation ◽  
Normal Expression ◽  
And Migration ◽  
Gsk 3Β ◽  
Migration Of Macrophages ◽  
Rho Kinases ◽  
Rock Activity

Abstract Rho kinases belong to a family of serine/threonine kinases whose role in recruitment and migration of inflammatory cells is poorly understood. We show that deficiency of ROCK1 results in increased recruitment and migration of macrophages and neutrophils in vitro and in vivo. Enhanced migration resulting from ROCK1 deficiency is observed despite normal expression of ROCK2 and a significant reduction in overall ROCK activity. ROCK1 directly binds PTEN in response to receptor activation and is essential for PTEN phosphorylation and stability. In the absence of ROCK1, PTEN phosphorylation, stability, and its activity are significantly impaired. Consequently, increased activation of downstream targets of PTEN, including PIP3, AKT, GSK-3β, and cyclin D1, is observed. Our results reveal ROCK1 as a physiologic regulator of PTEN whose function is to repress excessive recruitment of macrophages and neutrophils during acute inflammation.

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