scholarly journals Lipopolysaccharide Inhibits the Channel Activity of the P2X7 Receptor

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Elias Leiva-Salcedo ◽  
Claudio Coddou ◽  
Felipe E. Rodríguez ◽  
Antonello Penna ◽  
Ximena Lopez ◽  
...  
Keyword(s):  
Immune Response ◽  
P2x7 Receptor ◽  
T Regulatory Cells ◽  
Hek293 Cells ◽  
Erk Activation ◽  
Physiological Relevance ◽  
Purinergic P2x7 Receptor ◽  
Induced Apoptosis ◽  
Apoptosis And Necrosis ◽  
P2x7r Activation

The purinergic P2X7 receptor (P2X7R) plays an important role during the immune response, participating in several events such as cytokine release, apoptosis, and necrosis. The bacterial endotoxin lipopolysaccharide (LPS) is one of the strongest stimuli of the immune response, and it has been shown that P2X7R activation can modulate LPS-induced responses. Moreover, a C-terminal binding site for LPS has been proposed. In order to evaluate if LPS can directly modulate the activity of the P2X7R, we tested several signaling pathways associated with P2X7R activation in HEK293 cells that do not express the TLR-4 receptor. We found that LPS alone was unable to induce any P2X7R-related activity, suggesting that the P2X7R is not directly activated by the endotoxin. On the other hand, preapplication of LPS inhibited ATP-induced currents, intracellular calcium increase, and ethidium bromide uptake and had no effect on ERK activation in HEK293 cells. In splenocytes-derived T-regulatory cells, in which ATP-induced apoptosis is driven by the P2X7R, LPS inhibited ATP-induced apoptosis. Altogether, these results demonstrate that LPS modulates the activity of the P2X7R and suggest that this effect could be of physiological relevance.

scholarly journals Purinergic P2X7 Receptor Mediates the Elimination of Trichinella spiralis by Activating NF-κB/NLRP3/IL-1β Pathway in Macrophages

2021 ◽  
Vol 89 (5) ◽  
Author(s):  
Fei Guan ◽  
Wangfang Jiang ◽  
Yang Bai ◽  
Xiao Hou ◽  
Chunjie Jiang ◽  
...  
Keyword(s):  
Immune Response ◽  
P2x7 Receptor ◽  
Trichinella Spiralis ◽  
Vital Role ◽  
Content Type ◽  
Pyrin Domain ◽  
Purinergic P2x7 Receptor

ABSTRACT Trichinellosis is one of most neglected foodborne zoonoses worldwide. During Trichinella spiralis infection, the intestinal immune response is the first line of defense and plays a vital role in the host’s resistance. Previous studies indicate that purinergic P2X7 receptor (P2X7R) and pyrin domain-containing protein 3 (NLRP3) inflammasome are involved in the intestinal immune response in T. spiralis infection. However, the precise role of P2X7R and its effect on NLRP3 remains largely underdetermined. In this study, we aimed to investigate the role of P2X7R in the activation of NLRP3 in macrophages during the intestinal immune response against T. spiralis. We found that T. spiralis infection upregulated expression of P2X7R and activation of NLRP3 in macrophages in mice. In vivo, P2X7R deficiency resulted in increased intestinal adult and muscle larval burdens, along with decreased expression of NLRP3/interleukin-1β (IL-1β) in macrophages from the infected mice with T. spiralis. In In vitro experiments, P2X7R blockade inhibited activation of NLRP3/IL-1β via NF-κB and thus reduced the capacity of macrophages to kill newborn larvae of T. spiralis. These results indicate that P2X7R mediates the elimination of T. spiralis by activating the NF-κB/NLRP3/IL-1β pathway in macrophages. Our findings contribute to the understanding of the intestinal immune mechanism of T. spiralis infection.

scholarly journals TAMI-07. THE IMMUNE MICROENVIRONMENT IN LOWER GRADE GLIOMAS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii214-ii214
Author(s):  
Anupam Kumar ◽  
Katharine Chen ◽  
Claudia Petritsch ◽  
Theodore Nicolaides ◽  
Mariarita Santi-Vicini ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Cd8 T Cells ◽  
Molecular Mechanisms ◽  
T Regulatory Cells ◽  
Immune Cell ◽  
T Cell Response ◽  
Cytotoxic T Cell ◽  
Lower Grade ◽  
Functional Relationships

Abstract The determinants of the tumor-associated immune response in brain tumors are poorly understood. Using tumor samples from two molecularly distinct subtypes of lower grade glioma, MAPK-driven glioma with biallelic inactivation of CDKN2A (n=30) and IDH-mutant, 1p/19q-intact astrocytoma (n=29), we demonstrate qualitative and quantitative differences in the tumor-associated immune response and we investigate the molecular mechanisms involved. Histologically the MAPK-driven gliomas were comprised of pleomorphic xanthoastrocytoma (PXA) (n=11) and anaplastic PXA (n=19). Seven patients had paired samples from two sequential surgeries. Immune cell populations and their activity were determined by quantitative multiplex immunostaining and Digital Spatial Profiling and gene expression was analyzed by Nanostring. Functional studies were performed using established cell lines and two new patient-derived lines from MAPK-driven LGGs. MAPK-driven tumors exhibited an increased number of CD8+ T cells and tumor-associated microglial/macrophage (TAMs), including CD163+ TAMs, as compared to IDH-mutant astrocytoma. In contrast, IDH-mutant tumors had increased FOXP3+ immunosuppressive T regulatory cells. Transcriptional and protein level analyses in MAPK-driven tumors suggested an active cytotoxic T cell response with robust expression of granzyme B, present on 27% of CD8+ T cells, increased MHC class I expression, and altered cytokine profiles. Interestingly, MAPK-driven tumors also had increased expression of immunosuppressive molecules, including CXCR4, PD-L1, and VEGFA. Expression differences for cell surface and secreted proteins were confirmed in patient-derived tumor lines and functional relationships between altered chemokine expression and immune cell infiltration was investigated. Our data provide novel insights into the immune contexture of MAPK driven LGGs and suggest MAPK driven gliomas with biallelic inactivation of CDKN2A may be particularly vulnerable to immunotherapeutic modulation

scholarly journals ATP-induced cellular stress and mitochondrial toxicity in cells expressing purinergic P2X7 receptor

2015 ◽  
Vol 3 (2) ◽  
pp. e00123 ◽  
Author(s):  
Swen Seeland ◽  
Hélène Kettiger ◽  
Mark Murphy ◽  
Alexander Treiber ◽  
Jasmin Giller ◽  
...  
Keyword(s):  
P2x7 Receptor ◽  
Cellular Stress ◽  
Mitochondrial Toxicity ◽  
Purinergic P2x7 Receptor ◽  
In Cells

scholarly journals Irisin and Secondary Osteoporosis in Humans

2022 ◽  
Vol 23 (2) ◽  
pp. 690
Author(s):  
Roberta Zerlotin ◽  
Angela Oranger ◽  
Patrizia Pignataro ◽  
Manuela Dicarlo ◽  
Filippo Maselli ◽  
...  
Keyword(s):  
Mouse Models ◽  
Clinical Evidence ◽  
Bone Fractures ◽  
Secondary Osteoporosis ◽  
Men And Women ◽  
Physiological Relevance ◽  
Increased Risk ◽  
Induced Apoptosis ◽  
Circulating Levels

Irisin is a peptide secreted by skeletal muscle following exercise that plays an important role in bone metabolism. Numerous experiments in vitro and in mouse models have shown that the administration of recombinant irisin promotes osteogenesis, protects osteocytes from dexamethasone-induced apoptosis, prevents disuse-induced loss of bone and muscle mass, and accelerates fracture healing. Although some aspects still need to be elucidated, such as the dose- and frequency-dependent effects of irisin in cell cultures and mouse models, ample clinical evidence is emerging to support its physiological relevance on bone in humans. A reduction in serum irisin levels, associated with an increased risk of osteoporosis and bone fractures, was observed in postmenopausal women and in both men and women during aging, Recently, cohort studies of subjects with secondary osteoporosis showed that these patients have lower circulating levels of irisin, suggesting that this myokine could be a novel marker to monitor bone quality in this disease. Although there are still few studies, this review discusses the emerging data that are highlighting the involvement of irisin in some diseases that cause secondary osteoporosis.

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