Abstract:
:Inflammation is an important component of diabetic retinal damage. We previously reported that a novel β-adrenergic receptor agonist, Compound 49b, reduced Toll-like receptor 4 (TLR4) signaling in retinal endothelial cells (REC) grown in high glucose. Others reported that TLR4 activates high-mobility group box 1 (HMGB1), which has been associated with the NOD-like receptor 3 (NLRP3) inflammasome. Thus, we hypothesized that Epac1, a downstream mediator of β-adrenergic receptors, would block TLR4/HMGB1-mediated stimulation of the NLRP3 inflammasome, leading to reduced cleavage of caspase-1 and interleukin-1 beta (IL-1β). We generated vascular specific conditional knockout mice for Epac1 and used REC grown in normal and high glucose treated with an Epac1 agonist and/or NLRP3 siRNA. Protein analyses were done for Epac1, TLR4, HMGB1, NLRP3, cleaved caspase-1, and IL-1β. Loss of Epac1 in the mouse retinal vasculature significantly increased all of the inflammatory proteins. Epac1 effectively reduced high glucose-induced increases in TLR4, HMGB1, cleaved caspase-1, and IL-1β in REC. Taken together, the data suggest that Epac1 reduces formation of the NLRP3 inflammasome to reduce inflammatory responses in the retinal vasculature.
journal_name
Mediators Inflammjournal_title
Mediators of inflammationauthors
Jiang Y,Liu L,Curtiss E,Steinle JJdoi
10.1155/2017/2860956subject
Has Abstractpub_date
2017-01-01 00:00:00pages
2860956eissn
0962-9351issn
1466-1861journal_volume
2017pub_type
杂志文章abstract::The regulatory functions of glycosaminoglycan hyaluronan (HA) are suggested to be dependent on its molecular weight (MW). Proinflammatory and stimulatory effects are proposed mainly for the low MW HA. However, the complex response of blood phagocytes to HA of different MW is unclear. Herein, the effects of highly puri...
journal_title:Mediators of inflammation
pub_type: 杂志文章
doi:10.1155/2010/380948
更新日期:2010-01-01 00:00:00
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journal_title:Mediators of inflammation
pub_type: 杂志文章,评审
doi:10.1155/2019/4128682
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journal_title:Mediators of inflammation
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doi:10.1155/2017/4029641
更新日期:2017-01-01 00:00:00
abstract:BACKGROUND:Human and rodent leukocytes express high levels of the glucocorticoid-inducible protein annexin 1 (ANXA1) (previously referred to as lipocortin 1). Neutrophils and monocytes have abundant ANXA1 levels. AIM:We have investigated, for the first time, ANXA1 ultrastructural expression in rat eosinophils and comp...
journal_title:Mediators of inflammation
pub_type: 杂志文章
doi:10.1080/09629350210000015683
更新日期:2002-10-01 00:00:00
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journal_title:Mediators of inflammation
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doi:10.1155/2015/436572
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journal_title:Mediators of inflammation
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doi:10.1155/2009/850940
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journal_title:Mediators of inflammation
pub_type: 杂志文章,meta分析,评审
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更新日期:2015-01-01 00:00:00
abstract::[This corrects the article DOI: 10.1155/2020/6947482.]. ...
journal_title:Mediators of inflammation
pub_type: 已发布勘误
doi:10.1155/2020/2637019
更新日期:2020-11-21 00:00:00
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journal_title:Mediators of inflammation
pub_type: 杂志文章,评审
doi:10.1155/2015/820934
更新日期:2015-01-01 00:00:00
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journal_title:Mediators of inflammation
pub_type: 杂志文章
doi:10.1155/2018/3952526
更新日期:2018-10-08 00:00:00
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journal_title:Mediators of inflammation
pub_type: 杂志文章
doi:10.1155/2016/1062586
更新日期:2016-01-01 00:00:00
abstract::Background and Objectives. Malaria infection, caused by Plasmodium falciparum, is the most lethal and frequently culminates in severe clinical complications. Interleukin-22 (IL-22) has been implicated in several diseases including malaria. The objective of this study was to investigate the role of IL-22 gene polymorph...
journal_title:Mediators of inflammation
pub_type: 杂志文章
doi:10.1155/2020/5193723
更新日期:2020-02-19 00:00:00
abstract::Background. Neutrophilic bronchial inflammation is a main feature of bronchiectasis, but not much is known about its relationship with other disease features. Aim. To compare airway inflammatory markers with clinical and functional findings in subjects with stable noncystic fibrosis bronchiectasis (NCFB). Methods. 152...
journal_title:Mediators of inflammation
pub_type: 杂志文章
doi:10.1155/2015/642503
更新日期:2015-01-01 00:00:00
abstract::Previous studies showed little CD137 expressed in normal vascular smooth muscle cells (VSMCs) and it is important to find a valid way to elevate it before studying its function. The level of CD137 was detected by RT-PCR, western blot, and flow cytometry, respectively. CD137 signaling activation was activated by agonis...
journal_title:Mediators of inflammation
pub_type: 杂志文章
doi:10.1155/2017/1382805
更新日期:2017-01-01 00:00:00
abstract::Chemokines (CKs) and chemokine receptors (CKR) promote leukocyte recruitment into cardiac tissue infected by the Trypanosoma cruzi. This study investigated the long-term treatment with subantimicrobial doses of doxycycline (Dox) in association, or not, with benznidazole (Bz) on the expression of CK and CKR in cardiac ...
journal_title:Mediators of inflammation
pub_type: 杂志文章
doi:10.1155/2016/3694714
更新日期:2016-01-01 00:00:00
abstract:Objectives:To investigate the protective effect of ginsenoside Rg1 on relieving sepsis-induced lung inflammation and injury in vivo and in vitro. Methods:Cultured human pulmonary epithelial cell line A549 was challenged with LPS to induce cell injury, and CLP mouse model was generated to mimic clinical condition of sy...
journal_title:Mediators of inflammation
pub_type: 杂志文章
doi:10.1155/2019/6453296
更新日期:2019-02-24 00:00:00
abstract::Nitric oxide has enigmatic qualities in inflammation. In order to appreciate the precise contributions of nitric oxide to a pathophysiological process, one must account for enzyme source, coproduction of oxidants and antioxidant defences, time, rate of nitric oxide production, cellular source, peroxynitrite formation ...
journal_title:Mediators of inflammation
pub_type: 杂志文章
doi:10.1155/S0962935195000639
更新日期:1995-01-01 00:00:00
abstract::Thousands of people suffer from severe malaria every year. The innate immune response plays a determinant role in host's defence to malaria. Transient receptor potential vanilloid 1 (TRPV1) modulates macrophage-mediated responses in sepsis, but its role in other pathogenic diseases has never been addressed. We investi...
journal_title:Mediators of inflammation
pub_type: 杂志文章
doi:10.1155/2014/506450
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:The role of prolactin (PRL) on tissue injury and repair mechanisms in multiple sclerosis (MS) remains unclear. The aim of this work was to investigate the relationship between PRL plasma levels and brain damage as measured by magnetic resonance imaging (MRI). METHODS:We employed a chemiluminescence immunoas...
journal_title:Mediators of inflammation
pub_type: 杂志文章
doi:10.1155/2015/732539
更新日期:2015-01-01 00:00:00
abstract::The aim is to examine whether the changes in pleural fluid interleukin (IL)-1beta, IL-2, IL-6, and IL-8 levels were significant in differential diagnosis of childhood pleural effusions. IL-1beta, IL-2, IL-6, and IL-8 levels in pleural fluids of all 36 patients were measured. The levels of IL-1beta, IL-2, IL-6, and IL-...
journal_title:Mediators of inflammation
pub_type: 杂志文章
doi:10.1155/MI.2005.2
更新日期:2005-02-24 00:00:00
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pub_type: 杂志文章,评审
doi:10.1155/2016/3064643
更新日期:2016-01-01 00:00:00
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journal_title:Mediators of inflammation
pub_type: 杂志文章
doi:10.1155/S0962935194000256
更新日期:1994-01-01 00:00:00
abstract::The metabolic syndrome is a cluster of cardiometabolic alterations that include the presence of arterial hypertension, insulin resistance, dyslipidemia, and abdominal obesity. Obesity is associated with a chronic inflammatory response, characterized by abnormal adipokine production, and the activation of proinflammato...
journal_title:Mediators of inflammation
pub_type: 杂志文章,评审
doi:10.1155/2013/136584
更新日期:2013-01-01 00:00:00
abstract::Multiple sclerosis is an autoimmune disease with classical traits of demyelination, axonal damage, and neurodegeneration. The migration of autoimmune T cells and macrophages from blood to central nervous system as well as the destruction of blood brain barrier are thought to be the major processes in the development o...
journal_title:Mediators of inflammation
pub_type: 杂志文章,评审
doi:10.1155/2014/659206
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:Growth arrest specific gene 6 (Gas6) protein enhances survival of oligodendrocytes and neurons, and it is involved in autoimmunity. Therefore, we aimed to verify whether cerebrospinal-fluid (CSF) Gas6 concentration may represent a biomarker of disease activity in multiple sclerosis. METHODS:Sixty-five patie...
journal_title:Mediators of inflammation
pub_type: 杂志文章
doi:10.1155/2013/406483
更新日期:2013-01-01 00:00:00
abstract::Myeloproliferative neoplasms (MPNs) are a heterogeneous group of clonal diseases characterized by the excessive and chronic production of mature cells from one or several of the myeloid lineages. Recent advances in the biology of MPNs have greatly facilitated their molecular diagnosis since most patients present with ...
journal_title:Mediators of inflammation
pub_type: 杂志文章,评审
doi:10.1155/2015/145293
更新日期:2015-01-01 00:00:00
abstract:UNLABELLED:The aim of this study was to investigate the relationship between urinary eosinophil protein X (uEPX) and asthma symptoms, lung function, and other markers of eosinophilic airway inflammation in asthmatic school children. METHODS:A cross-sectional study was performed in 180 steroid dependent atopic children...
journal_title:Mediators of inflammation
pub_type: 杂志文章
doi:10.1155/2007/49240
更新日期:2007-01-01 00:00:00
abstract::High-fructose diet induced changes in gut microbiota structure and function, which have been linked to inflammatory response. However, the effect of small or appropriate doses of fructose on gut microbiota and inflammatory cytokines is not fully understood. Hence, the abundance changes of gut microbiota in fructose-tr...
journal_title:Mediators of inflammation
pub_type: 杂志文章
doi:10.1155/2020/6672636
更新日期:2020-11-30 00:00:00
abstract::Obesity-induced skeletal muscle inflammation is characterized by increased macrophage infiltration and inflammatory cytokine production. In this study, we investigated whether 4-1BB, a member of the TNF receptor superfamily (TNFRSF9) that provides inflammatory signals, participates in obesity-induced skeletal muscle i...
journal_title:Mediators of inflammation
pub_type: 杂志文章
doi:10.1155/2013/865159
更新日期:2013-01-01 00:00:00
abstract::Paraoxonase 1 (PON1) activity is markedly influenced by coding polymorphisms, Q/R at position 192 and M/L at position 55 of the PON1 gene. We investigated the frequencies of these polymorphisms and their effects on PON1 and antioxidant activities in 844 South African mixed ancestry individuals. Genotyping was done usi...
journal_title:Mediators of inflammation
pub_type: 杂志文章
doi:10.1155/2014/217019
更新日期:2014-01-01 00:00:00