Document Detail

TLR4: the receptor bridging Acanthamoeba challenge and intracellular inflammatory responses in human corneal cell lines.
MedLine Citation:
PMID:  20125114     Owner:  NLM     Status:  MEDLINE    
Acanthamoeba keratitis (AK) is a painful, vision-threatening infection caused by pathogenic strains of the protozoan, Acanthamoeba. Toll-like receptors (TLRs), which are important components of innate immunity, have an important role in the detection of foreign pathogens and the signaling cascades in host cells. However, no report on the interaction between Acanthamoeba and TLR has been found. In this study we analyzed the role of the TLR and its signaling pathway in human telomerase-immortalized corneal epithelial cells (HUCLs) and stromal fibroblasts (THSFs) challenged by Acanthamoeba. We show that the expressions of TLR4, myeloid differentiation protein 88 (MyD88), nuclear factor (NF)-kappaB, phospho-IkappaB, phospho-extracellular signal-regulated kinases 1/2 (p-Erk1/2) and the inflammatory cytokines interleukin (IL)-8, tumor necrosis factor (TNF)-alpha and interferon (IFN)-beta were significantly increased in Acanthamoeba-treated cells. Pretreatment with anti-TLR antibodies or the specific inhibitors pyrrolidine dithiocarbamate (PDTC) (for the NF-kappaB pathway) and U0126 (for the ERK pathway) was conducted. It was found that anti-TLR4 antibody attenuated the production of cytokines induced by Acanthamoeba infection. PDTC inhibited the production of IL-8 and TNF-alpha whereas U0126 inhibited the synthesis of IFN-beta. Thus, TLR4 is a receptor for Acanthamoeba and exerts an effect through TLR4-MyD88-NF-kappaB and TLR4-ERK1/2 pathways to induce the secretion of cytokines in human corneal cell lines challenged by Acanthamoeba.
Meiyu Ren; Li Gao; Xinyi Wu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-02-02
Journal Detail:
Title:  Immunology and cell biology     Volume:  88     ISSN:  1440-1711     ISO Abbreviation:  Immunol. Cell Biol.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-07-02     Completed Date:  2010-09-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8706300     Medline TA:  Immunol Cell Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  529-36     Citation Subset:  IM    
Department of Ophthalmology, Qilu Hospital, Shandong University, Jinan, China.
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MeSH Terms
Acanthamoeba / immunology
Acanthamoeba Keratitis / immunology*,  metabolism
Blotting, Western
Cell Line
Cytokines / biosynthesis,  immunology
Enzyme-Linked Immunosorbent Assay
Epithelium, Corneal / immunology*,  metabolism,  microbiology
Inflammation / immunology*,  metabolism,  microbiology
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction / immunology
Toll-Like Receptor 4 / immunology*,  metabolism
Reg. No./Substance:
0/Cytokines; 0/TLR4 protein, human; 0/Toll-Like Receptor 4

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