PMID- 20125114 OWN - NLM STAT- MEDLINE DCOM- 20100928 LR - 20180822 IS - 1440-1711 (Electronic) IS - 0818-9641 (Linking) VI - 88 IP - 5 DP - 2010 Jul TI - TLR4: the receptor bridging Acanthamoeba challenge and intracellular inflammatory responses in human corneal cell lines. PG - 529-36 LID - 10.1038/icb.2010.6 [doi] AB - 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. FAU - Ren, Meiyu AU - Ren M AD - Department of Ophthalmology, Qilu Hospital, Shandong University, Jinan, China. FAU - Gao, Li AU - Gao L FAU - Wu, Xinyi AU - Wu X LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100202 PL - United States TA - Immunol Cell Biol JT - Immunology and cell biology JID - 8706300 RN - 0 (Cytokines) RN - 0 (TLR4 protein, human) RN - 0 (Toll-Like Receptor 4) SB - IM MH - Acanthamoeba/immunology MH - Acanthamoeba Keratitis/*immunology/metabolism MH - Blotting, Western MH - Cell Line MH - Cytokines/biosynthesis/immunology MH - Enzyme-Linked Immunosorbent Assay MH - Epithelium, Corneal/*immunology/metabolism/microbiology MH - Humans MH - Inflammation/*immunology/metabolism/microbiology MH - Reverse Transcriptase Polymerase Chain Reaction MH - Signal Transduction/immunology MH - Toll-Like Receptor 4/*immunology/metabolism EDAT- 2010/02/04 06:00 MHDA- 2010/09/30 06:00 CRDT- 2010/02/04 06:00 PHST- 2010/02/04 06:00 [entrez] PHST- 2010/02/04 06:00 [pubmed] PHST- 2010/09/30 06:00 [medline] AID - icb20106 [pii] AID - 10.1038/icb.2010.6 [doi] PST - ppublish SO - Immunol Cell Biol. 2010 Jul;88(5):529-36. doi: 10.1038/icb.2010.6. Epub 2010 Feb 2.