Abstract:
:Corneal epithelial erosion is one of the most common problems in clinical ophthalmology. Despite significant progress in understanding how the cornea heals, clinically available pharmacological therapies that can promote repair and prevent visual complications remain limited. We have recently demonstrated that the acetylcholine (ACh) axis of corneal epithelium plays an important role in regulation and coordination of distinct activities of corneal epithelial cells (CEC) mediating re-epithelialization, but mechanisms remained unclear. We hypothesized that the grounds for synergistic effects of corneal ACh receptors lie within the signaling pathways linking different receptors to specific elements of the CEC pro-epithelialization activities. In this study, we sought to elucidate the molecular mechanisms of cooperation of corneal muscarinic and nicotinic ACh receptors (mAChRs and nAChRs) in upregulation of E-cadherin expression. The roles of individual corneal mAChRs and nAChRs subtypes were investigated by in-cell western assay of the ACh-treated CEC, in which different ACh receptor genes were silenced by receptor-specific shRNAs. Functional inactivation of M3, but not M4, mAChR subtype, or α3 or α7, but not α9, nAChR subunit significantly inhibited E-cadherin expression. To gain a mechanistic insight, we blocked the key steps of the downstream signaling pathways. Results demonstrated that cholinergic agonists can upregulate E-cadherin expression by activating M3 mAChR, and α3β2 and α7 nAChRs via the common signaling cascade Ca(2+)-CaMKII-PKC-Ras-Raf-MEK-ERK. Activation of α7 nAChR can launch the Ras-Raf-MEK-ERK cascade both indirectly, through the Ca(2+)-CaMKII-PKC step, and directly, perhaps, due to its direct interaction with Ras. Although the biological significance of such redundancy remained to be elucidated, results of the present study point to a new direction to pharmacologically accelerate corneal re-epithelialization, and should have salient clinical implication.
journal_name
Int Immunopharmacoljournal_title
International immunopharmacologyauthors
Chernyavsky AI,Galitovskiy V,Grando SAdoi
10.1016/j.intimp.2015.04.036subject
Has Abstractpub_date
2015-11-01 00:00:00pages
15-20issue
1eissn
1567-5769issn
1878-1705pii
S1567-5769(15)00200-3journal_volume
29pub_type
杂志文章abstract::Recombinant immunotoxins are chimeric proteins composed of a targeting peptide that binds to a specific tumor antigen and a toxin protein killing target cells. Recombinant immunotoxin exhibits potent cancer inhibiting effects both in vivo and in vitro. However, the non-specific toxicity causes severe syndromes limitin...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2018.11.039
更新日期:2019-01-01 00:00:00
abstract::Oral contraceptives (OC) may cause intrahepatic cholestasis or increase a pre-established liver damage. OC effects on hepatic injury biochemical markers remain contradictory and the role of cytokines in those processes is fairly unknown. Two doses, simple or double, of the OC combination ethinylestradiol/norgestrel we...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2014.03.022
更新日期:2014-07-01 00:00:00
abstract:BACKGROUND:Hepatic ischemia/reperfusion (I/R) injury occurs in different clinical settings as hepatic transplantation, and different types of shock. I/R injury is the main cause of hepatic damage and failure due to the production of reactive oxygen species (ROS) and inflammatory cytokines. Dimethyl fumarate (DMF), an i...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2019.106131
更新日期:2020-03-01 00:00:00
abstract::Streptococcus pyogenes is a common colonizer of the mucosal layers in the mouth, nose, and pharynx but it is also a major Gram-positive human pathogen that causes infections ranging from pharyngitis to severe systemic diseases. The lactobacilli colonize the oral tracts and are known to protect against colonization by ...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2013.07.005
更新日期:2013-10-01 00:00:00
abstract::High mobility group box 1 (HMGB1) has been identified to be a critical mediator of severe sepsis. Ketamine has been shown to reduce sepsis-induced pathological complications. These effects are because of the reduced expression and release of several inflammatory mediators. However, whether ketamine affects the express...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2014.08.003
更新日期:2014-11-01 00:00:00
abstract:OBJECTIVE:Inhaled corticosteroids (ICS) are generally used to treat patients with chronic obstructive pulmonary disease (COPD) who suffer from repeated exacerbations. Recently, it was reported that ICS treatment increased the risk of pneumonia in COPD patients. But it is controversial.The objective of this paper is to ...
journal_title:International immunopharmacology
pub_type: 杂志文章,meta分析
doi:10.1016/j.intimp.2019.105950
更新日期:2019-12-01 00:00:00
abstract::Influenza viruses cause significant morbidity and mortality and pose a substantial threat to public health. Vaccination represents the principle means of preventing influenza virus infection. Current vaccine approaches are hindered by the need to routinely reformulate vaccine compositions in an effort to account for t...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2018.07.011
更新日期:2018-10-01 00:00:00
abstract::In our previous study, we demonstrated that sesamolin can increase the level of cancer cell susceptibility to natural killer (NK) cell mediated cytolysis when it treats cancer cells. The present study attempted to demonstrate the direct influence of sesamolin on NK cells. To achieve the study goal, an NK cell (NK-92MI...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2018.08.027
更新日期:2018-11-01 00:00:00
abstract::High mobility group box protein 1 (HMGB1) and receptor for the advanced glycation end product (RAGE) play important roles in the development of sepsis-induced acute lung injury (ALI). Ketamine is considered to confer protective effects on ALI during sepsis. In this study, we investigated the effects of ketamine on HMG...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2016.01.021
更新日期:2016-05-01 00:00:00
abstract::Lipoteichoic acid (LTA) is a major virulence factor of Gram-positive bacteria including Staphylococcus aureus. Despite its pivotal role in causing sepsis, the systemic immune responses to LTA in human cells are poorly understood. Here, we produced highly-pure and structurally-intact LTA from S. aureus and examined the...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2012.05.010
更新日期:2012-08-01 00:00:00
abstract::The purpose of this study was the combination of curcumin and ovalbumin in free form or encapsulated into PLGA NPs (polylactic co-glycolic acid nanoparticles) to enhance their sublingual immunotherapy (SLIT) efficiency in mouse model of rhinitis allergic. PLGA NPs containing curcumin (CUR), ovalbumin (OVA) or both wer...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2020.106525
更新日期:2020-07-01 00:00:00
abstract:INTRODUCTION:Human recombinant interferon beta (IFN-β) is one of the first line treatments for Relapsing-Remitting Multiple Sclerosis (RRMS). However, the production of neutralizing antibodies (NAb) can impair its function. The aim of this study was to investigate the production of neutralizing antibodies against Rebif...
journal_title:International immunopharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.intimp.2018.06.032
更新日期:2018-09-01 00:00:00
abstract::Autism spectrum disorder (ASD) is a heterogeneous disorder diagnosed based on the severity of abnormalities in social skills. Several studies have acknowledged the presence of abnormal immune functions among individuals diagnosed with ASD. HLA-DR (human leukocyte antigen-antigen D related) has been shown to play a sig...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2018.10.027
更新日期:2018-12-01 00:00:00
abstract::Radiation exposure poses a significant threat to public health, which can lead to acute hematopoietic system and intestinal system injuries due to their higher radiation sensitivity. Hence, antioxidants and thiol-reducing agents could have a potential protective effect against this complication. The dithiol compound 1...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2019.105913
更新日期:2019-11-01 00:00:00
abstract::Cudratricusxanthone A (CTXA), isolated from the roots of Cudrania tricuspidata Bureau (Moraceae) has an isoprenylated xanthone skeleton that is known to exert a variety of biological activities. In the present study, we demonstrated that CTXA inhibited cyclooxygenase-2 (COX-2) and inducible nitric oxide (NO) synthase ...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2008.11.008
更新日期:2009-02-01 00:00:00
abstract::Acute lung injury (ALI) is one of the severe complications in patients with traumatic brain injury (TBI), contributing to the high mortality. Ghrelin has protective effects against various inflammatory diseases, but the effects of Ghrelin on TBI-induced ALI and its mechanisms remain unknown. In this study, Ghrelin adm...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2019.106175
更新日期:2020-02-01 00:00:00
abstract::Azithromycin (AZM) is a macrolide antibiotic that exhibits anti-inflammatory activity aside from its antimicrobial effect, a feature that may ameliorate certain inflammatory disorders and prevent graft-versus-host disease in patients receiving stem cell transplantation. In the present study, we investigated the abilit...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2016.09.012
更新日期:2016-11-01 00:00:00
abstract::The plasma kallikrein/kinin system that consists of the proteins factor XII, prekallikrein, and high molecular weight kininogen was first recognized as a surface-activated coagulation system arising when blood or plasma interacts with artificial surfaces. Although surface-activated contact activation occurs in vivo wh...
journal_title:International immunopharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.intimp.2007.08.022
更新日期:2008-02-01 00:00:00
abstract::Anti-nicotine vaccines comprise nicotine-like haptens conjugated to a carrier protein plus adjuvant(s). Unfortunately, those tested clinically have failed to improve overall long term quit rates. We had shown in mice that carrier, hapten, linker, hapten load (number of haptens per carrier molecule), aggregation and ad...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2015.09.012
更新日期:2015-12-01 00:00:00
abstract::Acute lung injury (ALI) is one of the most serious complications in critically ill patients which often leads to morbidity and mortality. ALI characterized by severe inflammation of lungs occurs due to uncontrolled inflammatory immune response. However, the immunological mechanism(s) are far from being understood. The...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2018.12.062
更新日期:2019-03-01 00:00:00
abstract::Despite the use of increasingly specific immunosuppressive therapy, rejection remains the leading cause of death in cardiac transplant patients. Endomyocardial biopsy (EMB) is the gold standard for early detection and monitoring of cardiac transplant rejection. However, this approach is invasive and not suitable for r...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2004.09.019
更新日期:2005-01-01 00:00:00
abstract::Upon activation, microglia release proinflammatory mediators that play important roles in eliciting neuroinflammatory responses associated with neurodegenerative diseases. The anti-inflammatory properties of eicosapentaenoic acid (EPA) have been known, however, the effects responsible for lipopolysaccharide (LPS)-indu...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2006.10.001
更新日期:2007-02-01 00:00:00
abstract::α-Cyperone is the volatile oil component in Cyperus rotundus L. The previous reports had shown the inhibition of α-Cyperone on NF-κB signaling in LPS-stimulated RAW264.7 cells. However, it is still unclear whether α-Cyperone could suppress inflammatory response in acute lung injury (ALI) induced by LPS. The aim of thi...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2019.105886
更新日期:2019-11-01 00:00:00
abstract:OBJECTIVE:Increases in galactose-deficient IgA1 (Gd-IgA1) play a crucial role in the pathogenesis of IgA nephropathy (IgAN), and several recent experiments have shown that microRNAs (miRNAs) are involved in regulating the development and physiological function of the kidney. The aims of this study were to identify miRN...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2020.106362
更新日期:2020-02-29 00:00:00
abstract::Our previous findings demonstrated that chlorophyllin (CHL) inhibits inducible nitric oxide gene expression in macrophages. In the present study, we show that CHL inhibited IL-1beta production and its mRNA expression in a lipopolysaccharide (LPS)-stimulated murine macrophage cell-line, RAW 264.7. The inhibitory effect...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2005.08.012
更新日期:2006-02-01 00:00:00
abstract:BACKGROUND:Downregulation of histone deacetylase-4 (HDAC4) contributes to cartilage degeneration in osteoarthritis (OA) because it promotes upregulation of runt-related transcription factor-2 (Runx-2) and osteoarthritis-related genes. The effect of HDAC4 upregulation on cartilage damage in OA remains unknown. METHODS:...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2019.105752
更新日期:2019-10-01 00:00:00
abstract:OBJECTIVES:To investigate the effects of neutrophil extracellular traps (NETs) on angiogenesis in vitro and in vivo and the regulatory role of mammalian target of rapamycin (mTOR) activity in it. METHODS:The regulatory role of mTOR in NETs formation was explored. In vitro, human neutrophils were pretreated with rapamy...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2020.106902
更新日期:2020-11-01 00:00:00
abstract::Spinal cord injury (SCI) is considered to be primarily associated with loss of motor function and leads to the activation of diverse cellular mechanisms in the central nervous system to attempt to repair the damaged spinal cord tissue. Higenamine (HG) (1-[(4-hydroxyphenyl) methyl]-1,2,3,4-tetrahydroisoquinoline-6,7-di...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2014.10.022
更新日期:2014-12-01 00:00:00
abstract::We previously reported that abnormally down-regulated protein kinase C (PKC) activity is responsible for the impaired cellular function of natural killer cells and polymorphonuclear cells (PMNs), and the giant granule formation in fibroblasts in the beige mouse, an animal model of Chediak-Higashi syndrome. Here, we ex...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2007.03.004
更新日期:2007-07-01 00:00:00
abstract::Acetylcholine (ACh) acts as a local cellular signaling molecule and is widely expressed in nature, including mammalian cells and embryonic stem cells. The murine embryonic stem cell line CGR8 synthesizes and releases substantial amounts of ACh. Particularly during early differentiation - a period associated with multi...
journal_title:International immunopharmacology
pub_type: 杂志文章
doi:10.1016/j.intimp.2015.04.005
更新日期:2015-11-01 00:00:00