Green Tea Extract Treatment Alleviates Ocular Inflammation in a Rat Model of Endotoxin-Induced Uveitis

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Green tea extract (GTE) ingested by rats exerted anti-oxidative activities in various ocular tissues as shown in our previous studies. The present work investigated anti-inflammatory effects of GTE on endotoxin-induced uveitis (EIU). EIU was generated in adult rats by a footpad injection of 1 mg/kg lipopolysaccharide (LPS). Oral administration of GTE (550 mg/kg) was given one, two or four times after LPS injection. Twenty-four hours later, LPS produced severe hyperemia and edema in the iris. Immunocytochemical examinations showed an accumulation of infiltrating cells in the aqueous humor that were immunopositive for cluster of differentiation 43 (CD43) and CD68, markers for leucocytes and macrophages, respectively. Analyses of the aqueous humor showed an increase in pro-inflammatory mediators including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1). GTE treatments improved the clinical manifestations and reduced infiltrating cells and protein exudation in the aqueous humor, which were not observed under half dose of GTE (275 mg/kg). The number of CD68 positive macrophages residing in the iris and ciliary was also reduced. GTE suppressed production of TNF-α, IL-6 and MCP-1 in the aqueous humor, which was associated with a down-regulation of LPS receptor complex subunits, Toll-like receptor 4 (TLR-4) and CD14, and suppression of nuclear factor-kappa Bp65 (NF-κBp65) in the iris and ciliary body. Our findings show that GTE is a potent anti-inflammatory agent against the inflammation of EIU, and suggest a potential use in treatment of acute uveitis.

Related collections

Most cited references 38

Record: found
Abstract: found
Article: not found

Incidence and prevalence of uveitis in Northern California; the Northern California Epidemiology of Uveitis Study.

David C. Gritz, Ira G. Wong (2004)

To determine the incidence and prevalence of uveitis in a large, well-defined population in Northern California. Cross-sectional study using retrospective database and medical record review. A group of 2070 people within 6 Northern California medical center communities (N = 731 898) who had a potential diagnosis of uveitis. The patient database of a large health maintenance organization (2 805 443 members at time of the study) was searched for all patients who, during a 12-month period, had the potential diagnosis of uveitis. Detailed quarterly gender- and age-stratified population data were available. Medical records of patients who potentially had uveitis and who were members of the 6 target communities were reviewed by 2 uveitis subspecialists to confirm the diagnosis of uveitis and to establish time of onset. Demographic and clinical data were gathered for patients meeting the clinical definition of uveitis. Incidence rates were calculated by using a dynamic population model. Prevalence rates were based on the mid-study period population. Presence and date of onset of uveitis. At midstudy, the population for the 6 communities was 731 898. During the target period, 382 new cases of uveitis were diagnosed; 462 cases of uveitis were diagnosed before the target period. These data yielded an incidence of 52.4/100 000 person-years and a period prevalence of 115.3/100 000 persons. The incidence and prevalence of disease were lowest in pediatric age groups and were highest in patients 65 years or older (P<0.0001). The prevalence of uveitis was higher in women than in men (P<0.001), but the difference in incidence between men and women was not statistically significant. Comparison between the group of patients who had onset of uveitis before the target period (ongoing uveitis) and the entire cohort of uveitis patients showed that women had a higher prevalence of ongoing uveitis than men and that this difference was largest in the older age groups (P<0.001). In this largest population-based uveitis study in the United States to date, the incidence of uveitis was approximately 3 times that of previous U.S. estimates and increased with the increasing age of patients. Women had a higher prevalence of uveitis than men, and the largest differences were in older age groups.

0 comments Cited 200 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Lipopolysaccharide recognition: CD14, TLRs and the LPS-activation cluster.

Martha Triantafilou, Kathy Triantafilou (2002)

Recognition of bacterial lipopolysaccharide (LPS) by the innate immune system elicits strong pro-inflammatory responses that can eventually cause a fatal sepsis syndrome in humans. LPS-mediated activation of mammalian cells is believed to involve the interaction of LPS with lipopolysaccharide-binding protein (LBP) in the serum and, subsequently with CD14. Although there is no doubt that CD14 binds LPS, CD14 is not capable of initiating a transmembrane activation signal because it is a glycosylphosphatidylinositol (GPI)-anchored protein. Accumulating evidence has suggested that LPS must interact with a transmembrane receptor(s) that is responsible for signal transduction. Integrins CD11c and/or CD18, Toll-like receptors (TLRs), as well as CD55, have been suggested to serve this function. Recently, we have revealed that a signalling complex of receptors is formed following LPS stimulation, which comprises heat-shock proteins (Hsps) 70 and 90, chemokine receptor 4 (CXCR4) and growth differentiation factor 5 (GDF5). Taking into account the discovery of the TLRs and the LPS-activation cluster, we propose a new model of LPS recognition.

0 comments Cited 155 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Heme activates TLR4-mediated inflammatory injury via MyD88/TRIF signaling pathway in intracerebral hemorrhage

Qing-Wu Yang, Sen Lin, Qing Yin … (2012)

Background Inflammatory injury plays a critical role in intracerebral hemorrhage (ICH)-induced neurological deficits; however, the signaling pathways are not apparent by which the upstream cellular events trigger innate immune and inflammatory responses that contribute to neurological impairments. Toll-like receptor 4 (TLR4) plays a role in inflammatory damage caused by brain disorders. Methods In this study, we investigate the role of TLR4 signaling in ICH-induced inflammation. In the ICH model, a significant upregulation of TLR4 expression in reactive microglia has been demonstrated using real-time RT-PCR. Activation of microglia was detected by immunohistochemistry, cytokines were measured by ELISA, MyD88, TRIF and NF-κB were measured by Western blot and EMSA, animal behavior was evaluated by animal behavioristics. Results Compared to WT mice, TLR4−/− mice had restrained ICH-induced brain damage showing in reduced cerebral edema and lower neurological deficit scores. Quantification of cytokines including IL-6, TNF-α and IL-1β and assessment of macrophage infiltration in perihematoma tissues from TLR4−/−, MyD88−/− and TRIF−/− mice showed attenuated inflammatory damage after ICH. TLR4−/− mice also exhibited reduced MyD88 and TRIF expression which was accompanied by decreased NF-κB activity. This suggests that after ICH both MyD88 and TRIF pathways might be involved in TLR4-mediated inflammatory injury possibly via NF-κB activation. Exogenous hemin administration significantly increased TLR4 expression and microglial activation in cultures and also exacerbated brain injury in WT mice but not in TLR4−/− mice. Anti-TLR4 antibody administration suppressed hemin-induced microglial activation in cultures and in the mice model of ICH. Conclusions Our findings suggest that heme potentiates microglial activation via TLR4, in turn inducing NF-κB activation via the MyD88/TRIF signaling pathway, and ultimately increasing cytokine expression and inflammatory injury in ICH. Targeting TLR4 signaling may be a promising therapeutic strategy for ICH.

0 comments Cited 125 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Anand Swaroop: Role: Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS ONE

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, USA )

ISSN (Electronic): 1932-6203

Publication date Collection: 2014

Publication date (Electronic): 5 August 2014

Volume: 9

Issue: 8

Electronic Location Identifier: e103995

Affiliations

[1 ]Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong

[2 ]School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China

National Eye Institute, United States of America

Author notes

* E-mail: cppang@ 123456cuhk.edu.hk (CPP); sunonchan@ 123456cuhk.edu.hk (SOC)

Competing Interests: The authors have declared that no competing interests exist.

Conceived and designed the experiments: CPP SOC KOC. Performed the experiments: YJQ YWYY WYL YPY KPC JLR. Analyzed the data: YJQ YWYY WYL. Contributed reagents/materials/analysis tools: WYL YPY KPC. Wrote the paper: YJQ CPP SOC KOC.

Article

Publisher ID: PONE-D-14-02072

DOI: 10.1371/journal.pone.0103995

PMC ID: 4122397

PubMed ID: 25093862

SO-VID: a71549b3-6a89-47ea-9c2b-d2686fba6250

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

History

Date received : 15 January 2014

Date accepted : 6 July 2014

Page count

Pages: 12

Funding

This work was supported in part by a block grant of the University Grants Committee Hong Kong, a GRF Grant (Project No. CUHK461612), a seed grant from Lui Che Woo Institute of Innovative Medicine (Project No. 8303107) and the Endowment Fund for Lim Por-Yen Eye Genetics Research Centre, Hong Kong. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Green Tea Extract Treatment Alleviates Ocular Inflammation in a Rat Model of Endotoxin-Induced Uveitis

Read this article at

Abstract

Related collections

PLOS Climate

Most cited references 38

Incidence and prevalence of uveitis in Northern California; the Northern California Epidemiology of Uveitis Study.

Lipopolysaccharide recognition: CD14, TLRs and the LPS-activation cluster.

Heme activates TLR4-mediated inflammatory injury via MyD88/TRIF signaling pathway in intracerebral hemorrhage

Author and article information

Contributors

Journal

Affiliations

Author notes

Article

History

Page count

Funding

Categories

Comments

Comment on this article

Similar content 127

Cited by 15

Most referenced authors 549