Platelets as Modulators of Inflammation

2017 ◽  
Vol 44 (02) ◽  
pp. 091-101 ◽  
Author(s):  
Seok-Joo Kim ◽  
Rachelle Davis ◽  
Craig Jenne
Keyword(s):  
Endothelial Cell ◽  
Tissue Damage ◽  
Inflammatory Responses ◽  
Platelet Response ◽  
Platelet Activity ◽  
Disease Pathogenesis ◽  
Innate And Adaptive Immunity ◽  
Effector Cells ◽  
Cell Responses

AbstractPlatelets have classically been considered crucial effector cells in hemostasis, but now are increasingly recognized as players during inflammatory responses in innate and adaptive immunity. Platelets can recognize and kill invading pathogens, and, upon stimulation, also release a wide array of mediators that modify immune and endothelial cell responses. Increased platelet activity can protect the host against infectious insults; however, the excessive activity can lead to inflammation-mediated tissue damage. These critical roles highlight the necessity of balancing the platelet response at the intersection of hemostasis and inflammation. In this review, the authors present the current understanding of the inflammatory role of platelets. They also highlight recent findings on a modulator that links inflammation and deleterious tissue damage in disease pathogenesis.

Role of Calcium in Receptor-mediated Endothelial Cell Responses

CHEST Journal ◽  
1988 ◽  
Vol 93 (3) ◽  
pp. 105S-109S ◽  
Author(s):  
Una S. Ryan ◽  
Anthony Johns ◽  
Cornelis Van Breemen
Keyword(s):  
Endothelial Cell ◽  
Cell Responses

scholarly journals Injured liver-released miRNA-122 elicits acute pulmonary inflammation via activating alveolar macrophage TLR7 signaling pathway

2019 ◽  
Vol 116 (13) ◽  
pp. 6162-6171 ◽  
Author(s):  
Yanbo Wang ◽  
Hongwei Liang ◽  
Fangfang Jin ◽  
Xin Yan ◽  
Guifang Xu ◽  
...  
Keyword(s):  
Liver Injury ◽  
Alveolar Macrophage ◽  
Tissue Damage ◽  
Inflammatory Responses ◽  
Pulmonary Inflammation ◽  
Underlying Mechanism ◽  
Causative Role ◽  
Independent Manner ◽  
Liver Injuries

Hepatic injury is often accompanied by pulmonary inflammation and tissue damage, but the underlying mechanism is not fully elucidated. Here we identify hepatic miR-122 as a mediator of pulmonary inflammation induced by various liver injuries. Analyses of acute and chronic liver injury mouse models confirm that liver dysfunction can cause pulmonary inflammation and tissue damage. Injured livers release large amounts of miR-122 in an exosome-independent manner into the circulation compared with normal livers. Circulating miR-122 is then preferentially transported to mouse lungs and taken up by alveolar macrophages, in which it binds Toll-like receptor 7 (TLR7) and activates inflammatory responses. Depleting miR-122 in mouse liver or plasma largely abolishes liver injury-induced pulmonary inflammation and tissue damage. Furthermore, alveolar macrophage activation by miR-122 is blocked by mutating the TLR7-binding GU-rich sequence on miR-122 or knocking out macrophage TLR7. Our findings reveal a causative role of hepatic miR-122 in liver injury-induced pulmonary dysfunction.

scholarly journals Role of Mitochondrial Oxidant Generation in Endothelial Cell Responses to Hypoxia

2002 ◽  
Vol 22 (4) ◽  
pp. 566-573 ◽  
Author(s):  
Daryl P. Pearlstein ◽  
Mir H. Ali ◽  
Paul T. Mungai ◽  
Karen L. Hynes ◽  
Bruce L. Gewertz ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Responses

scholarly journals Dnmt3arestrains mast cell inflammatory responses

2017 ◽  
Vol 114 (8) ◽  
pp. E1490-E1499 ◽  
Author(s):  
Cristina Leoni ◽  
Sara Montagner ◽  
Andrea Rinaldi ◽  
Francesco Bertoni ◽  
Sara Polletti ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Mast Cell ◽  
Cell Biology ◽  
Dna Methyltransferase ◽  
Cell Activation ◽  
Inflammatory Responses ◽  
Mast Cell Activation ◽  
Cell Responses

DNA methylation and specifically the DNA methyltransferase enzyme DNMT3A are involved in the pathogenesis of a variety of hematological diseases and in regulating the function of immune cells. Although altered DNA methylation patterns and mutations inDNMT3Acorrelate with mast cell proliferative disorders in humans, the role of DNA methylation in mast cell biology is not understood. By using mast cells lackingDnmt3a, we found that this enzyme is involved in restraining mast cell responses to acute and chronic stimuli, both in vitro and in vivo. The exacerbated mast cell responses observed in the absence ofDnmt3awere recapitulated or enhanced by treatment with the demethylating agent 5-aza-2′-deoxycytidine as well as by down-modulation ofDnmt1expression, further supporting the role of DNA methylation in regulating mast cell activation. Mechanistically, these effects were in part mediated by the dysregulated expression of the scaffold protein IQGAP2, which is characterized by the ability to regulate a wide variety of biological processes. Altogether, our data demonstrate that DNMT3A and DNA methylation are key modulators of mast cell responsiveness to acute and chronic stimulation.

The Role of Endothelial Cell Injury and Platelet Response in Atherogenesis

1978 ◽  
Vol 39 (02) ◽  
pp. 312-321 ◽  
Author(s):  
Laurence A Harker ◽  
Russell Ross ◽  
John A Glomset
Keyword(s):  
Endothelial Cell ◽  
Cell Injury ◽  
Platelet Response ◽  
Endothelial Cell Injury

scholarly journals Role of Integrin β4 in Lung Endothelial Cell Inflammatory Responses to Mechanical Stress

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Weiguo Chen ◽  
Yulia Epshtein ◽  
Xiuquin Ni ◽  
Randal O. Dull ◽  
Anne E. Cress ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Mechanical Stress ◽  
Inflammatory Responses ◽  
Integrin Β4

Role of nuclear IκBs in inflammation regulation

2013 ◽  
Vol 4 (2) ◽  
pp. 187-196 ◽  
Author(s):  
Tomoki Chiba ◽  
Hidetoshi Inoko ◽  
Minoru Kimura ◽  
Takehito Sato
Keyword(s):  
Autoimmune Diseases ◽  
Inflammatory Responses ◽  
Susceptibility Gene ◽  
Nuclear Factor Κb ◽  
Nuclear Entry ◽  
Genetic Studies ◽  
Innate And Adaptive Immunity ◽  
Excessive Activation ◽  
Transcription Factor Nuclear Factor

AbstractA wide variety of environmental cues, including inflammatory cytokines, ligands for pattern recognition receptors and endogenous danger signals, activate the inducible transcription factor nuclear factor-κB (NF-κB), which is a central regulator of inflammatory and immune responses. Excessive activation of NF-κB results in the development of severe diseases, such as chronic inflammatory disorders, autoimmune diseases and cancer. Therefore, the transcriptional activity of NF-κB is tightly regulated at multiple steps. One mechanism is mediated by the inhibitor of κB (IκB), a well-defined regulator of NF-κB that resides in the cytoplasm and prevents NF-κB from nuclear entry by sequestration. Recently, several atypical IκBs that reside in the nucleus were identified: Bcl-3, IκBζ, IκBNS and IκBη. In contrast to conventional IκBs, these atypical IκBs positively and negatively modulate NF-κB-mediated transcription. The function of atypical IκBs is independent of the prevention of NF-κB nuclear entry. Therefore, atypical IκBs are considered distinct from conventional IκBs and have been termed ‘nuclear IκBs.’ In addition to these members, our recent study indicated that IκBL, originally reported as a susceptibility gene for rheumatoid arthritis, also serves as a nuclear IκB. Biological and genetic studies strongly suggest that nuclear IκBs play important roles in the pathogenesis of inflammatory and autoimmune diseases via the regulation of both innate and adaptive immunity. In this review, we discuss the recent advances in our understanding of nuclear IκBs in the context of NF-κB-mediated transcriptional regulation and inflammatory responses.

scholarly journals Functional evidence for epitope spreading in the relapsing pathology of experimental autoimmune encephalomyelitis.

1995 ◽  
Vol 182 (1) ◽  
pp. 75-85 ◽  
Author(s):  
B L McRae ◽  
C L Vanderlugt ◽  
M C Dal Canto ◽  
S D Miller
Keyword(s):  
T Cells ◽  
T Cell ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Tissue Damage ◽  
Acute Disease ◽  
Epitope Spreading ◽  
Autoimmune Encephalomyelitis ◽  
Cell Responses ◽  
Experimental Autoimmune

The role of epitope spreading in the pathology of relapsing-remitting experimental autoimmune encephalomyelitis (R-EAE) was examined. Using peripherally induced immunologic tolerance as a probe to analyze the neuropathologic T cell repertoire, we show that the majority of the immunopathologic reactivity during the acute phase of R-EAE in SJL/J mice induced by active immunization with the intact proteolipid (PLP) molecule is directed at the PLP139-151 epitope and that responses to secondary encephalitogenic PLP epitopes may contribute to the later relapsing phases of disease. Intermolecular epitope spreading was demonstrated by showing the development of T cell responses to PLP139-151 after acute disease in mice in which R-EAE was initiated by the transfer of T cells specific for the non-cross-reactive MBP84-104 determinant. Intramolecular epitope spreading was demonstrated by showing that endogenous host T cells specific for a secondary encephalitogenic PLP epitope (PLP178-191) are demonstrable by both splenic T cell proliferative and in vivo delayed-type hypersensitivity responses in mice in which acute central nervous system damage was initiated by T cells reactive with the immunodominant, non-cross-reactive PLP139-151 sequence. The PLP178-191-specific responses are activated as a result of and correlate with the degree of acute tissue damage, since they do not develop in mice tolerized to the initiating epitope before expression of acute disease. Most importantly, we show that the PLP178-191-specific responses are capable of mediating R-EAE upon adoptive secondary transfer to naive recipient mice. Furthermore, induction of tolerance to intact PLP (which inhibits responses to both the initiating PLP139-151 epitope and to the PLP178-191 epitope) after the acute disease episode is sufficient to prevent relapsing disease. These results strongly support a contributory role of T cell responses to epitopes released as a result of acute tissue damage to the immunopathogenesis of relapsing clinical episodes and have important implications for the design of antigen-specific immunotherapies for the treatment of chronic autoimmune disorders in humans.

ID: 126: ROLE OF SYNDECAN-1 IN MECHANICAL STRESS-INDUCED LUNG ENDOTHELIAL CELL INFLAMMATORY RESPONSES MEDIATED BY INTEGRIN BETA4

2016 ◽  
Vol 64 (4) ◽  
pp. 972.2-973
Author(s):  
W Chen ◽  
RO Dull ◽  
JR Jacobson
Keyword(s):  
Endothelial Cell ◽  
Lung Injury ◽  
Mechanical Stress ◽  
Tyrosine Phosphorylation ◽  
Western Blotting ◽  
Inflammatory Responses ◽  
Cyclic Stretch ◽  
Protective Effects ◽  
Coa Reductase

RationaleSimvastatin, an HMG-CoA reductase inhibitor, has protective effects on mechanically stressed human lung endothelial cells (EC) that are mediated by the attenuation of agonist-induced integrin β4 (ITGB4) tyrosine phosphorylation. In addition, overexpression of ITGB4 constructs harboring mutations in tyrosine phosphorylation sites within the cytoplasmic tail results in decreased mechanical stress-induced inflammatory cytokine release by EC. However, the mechanisms by which ITGB4 phosphorylation is regulated is unknown. A molecule of interest in this context is syndecan-1, a cell-surface proteoglycan that binds extraceullar matrix components but also binds the ITGB4 cytoplasmic domain, is expressed by EC, and has been implicated as a mediator of acute lung injury (ALI). Thus, we hypothesized that syndecan-1 is an effector of lung endothelial cell inflammatory responses mediated by ITGB4 in response to mechanical stress.MethodsTo investigate the effects of simvastatin on ITGB4 and syndecan-1 expression human pulmonary artery EC lysates treated with simvastatin (5 µM, 16 h) were subjected to Western blotting for ITGB4 and syndecan-1. Simvastatin-treated EC were then used for immunoprecipitation (IP) of syndecan-1 followed by Western blotting for ITGB4. To study the role of syndecan-1 in EC inflammatory responses to mechanical stress mediated by ITGB4, EC were transfected with syndecan-1 siRNA prior to cyclic stretch (18% CS) and lysates were collected for immunoprecipitation of ITGB4 followed by Western blotting with a phospho-tyrosine antibody. Finally, syndecan-1-silenced EC were subjected to 18% CS and the media was collected for measurement of IL-6 and IL-8 levels.ResultsSimvastatin treatment of EC resulted in both a dramatic increase in ITGB4 and a marked decreased in syndecan-1 expression levels. In addition, syndecan-1 association with ITGB4 was markedly decreased in EC treated with simvastatin. In EC subjected to 18% CS, ITGB4 phosphorylation was significantly decreased after syndecan-1 knockdown. Finally, silencing of syndecan-1 was associated with a significant decrease in CS-induced EC IL-6 and IL-8 expression (76% and 66%, respectively, p<0.05 for both).ConclusionOur results implicate syndecan-1 as an important mediator of EC ITGB4 tyrosine phosphorylation affected by both simvastatin and mechanical-stress. These findings represent a novel area of investigation that may ultimately yield new therapeutic targets and strategies for patients with ventilator-induced lung injury, a form of ALI precipitated by excessive lung stretch.

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