RGD Reference Report - Toll-like receptor 4 signalling pathway activation in a rat model of Acanthamoeba Keratitis. - Rat Genome Database

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Toll-like receptor 4 signalling pathway activation in a rat model of Acanthamoeba Keratitis.

Authors: Ren, MY  Wu, XY 
Citation: Ren MY and Wu XY, Parasite Immunol. 2011 Jan;33(1):25-33. doi: 10.1111/j.1365-3024.2010.01247.x.
RGD ID: 7777095
Pubmed: PMID:21155840   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1365-3024.2010.01247.x   (Journal Full-text)

The pathogenesis of Acanthamoeba keratitis (AK) is complicated. In our previous studies, TLR4 was found involved in the process of infection by Acanthamoeba in human corneal cells. The purpose of this study was to investigate the role of Toll-like receptor 4 (TLR4) signalling pathway in Wistar rats challenged with Acanthamoeba. The rat model of AK was established. Corneas were collected and analysed by real-time PCR to assess the mRNA levels of TLR 2, 4, myeloid differentiation protein (MyD)88, nuclear factor (NF)-kappaB, extracellular signal-regulated kinase (ERK), interleukin (IL)-8, tumour necrosis factor (TNF)-alpha and interferon (IFN) -beta. Immunocytochemistry and Western blot were conducted to examine the proteins of TLR2, TLR4, p-Erk1/2 and p-IkappaB. Specific inhibitors PDTC and U0126 were used to pretreat the animals to determine the exact receptor and signalling pathway involved in pathogenesis. Expressions of TLR4, MyD88, all three cytokines, NF-kappaB, p-IkappaB and p-Erk1/2 were increased in Acanthamoeba-treated rat corneas. PDTC inhibited the production of IL-8 and TNF-alpha, while U0126 inhibited the synthesis of IFN-beta. TLR4 was involved in sensing the challenge of Acanthamoeba and inducing production of cytokines through TLR4-NF-kappaB and TLR4-Erk1/2 pathways in corneas of Wistar rats.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Acanthamoeba Keratitis  ISOTlr4 (Rattus norvegicus)7777095; 7777095mRNA and protein:increased expression:corneaRGD 
Acanthamoeba Keratitis  IEP 7777095mRNA and protein:increased expression:corneaRGD 

Objects Annotated

Genes (Rattus norvegicus)
Tlr4  (toll-like receptor 4)

Genes (Mus musculus)
Tlr4  (toll-like receptor 4)

Genes (Homo sapiens)
TLR4  (toll like receptor 4)


Additional Information