Toll-like receptors in ocular immunity and the immunopathogenesis of inflammatory eye disease

Chang, John H; McCluskey, Peter; Wakefield, Denis

doi:10.1136/bjo.2005.072686

Cited by 156 publications

(133 citation statements)

References 36 publications

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“…AnxA1 expression was observed in the epithelia of the cornea, iris, ciliary processes, and retina in all of the groups, and it occurred in the same regions where TLR4 expression is observed (10)(11)(12). In uveitis, cytokines and NO are produced mainly by inflammatory and endothelial cells, but these mediators can also be released by the epithelial cells of the cornea and RPE (40), consistent with the sites of AnxA1 expression.…”

Section: Effects Of Anxa1 On Il-6 Il-8 and Cox-2 Gene Expression Insupporting

confidence: 49%

“…In this model, LPS binds to TLR4 on eye cells (10)(11)(12) and stimulates the synthesis and release of proinflammatory chemical mediators, such as NO, platelet-activating factor, TNFa, IL-1b, and other cytokines (9,10). The most commonly activated pathway in this model is that of NF-kB, which is followed by its translocation from the cytoplasm to the nucleus (9,13).…”

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confidence: 99%

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Anti-Inflammatory Mechanisms of the Annexin A1 Protein and Its Mimetic Peptide Ac2-26 in Models of Ocular Inflammation In Vivo and In Vitro

Girol

Mimura

Drewes

et al. 2013

The Journal of Immunology

103

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Annexin A1 (AnxA1) is a protein that displays potent anti-inflammatory properties, but its expression in eye tissue and its role in ocular inflammatory diseases have not been well studied. We investigated the mechanism of action and potential uses of AnxA1 and its mimetic peptide (Ac2-26) in the endotoxin-induced uveitis (EIU) rodent model and in human ARPE-19 cells activated by LPS. In rats, analysis of untreated EIU after 24 and 48 h or EIU treated with topical applications or with a single s.c. injection of Ac2-26 revealed the anti-inflammatory actions of Ac2-26 on leukocyte infiltration and on the release of inflammatory mediators; the systemic administration of Boc2, a formylated peptide receptor (fpr) antagonist, abrogated the peptide’s protective effects. Moreover, AnxA1−/− mice exhibited exacerbated EIU compared with wild-type animals. Immunohistochemical studies of ocular tissue showed a specific AnxA1 posttranslational modification in EIU and indicated that the fpr2 receptor mediated the anti-inflammatory actions of AnxA1. In vitro studies confirmed the roles of AnxA1 and fpr2 and the protective effects of Ac2-26 on the release of chemical mediators in ARPE-19 cells. Molecular analysis of NF-κB translocation and IL-6, IL-8, and cyclooxygenase-2 gene expression indicated that the protective effects of AnxA1 occur independently of the NF-κB signaling pathway and possibly in a posttranscriptional manner. Together, our data highlight the role of AnxA1 in ocular inflammation, especially uveitis, and suggest the use of AnxA1 or its mimetic peptide Ac2-26 as a therapeutic approach.

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Section: Effects Of Anxa1 On Il-6 Il-8 and Cox-2 Gene Expression Insupporting

confidence: 49%

mentioning

confidence: 99%

Anti-Inflammatory Mechanisms of the Annexin A1 Protein and Its Mimetic Peptide Ac2-26 in Models of Ocular Inflammation In Vivo and In Vitro

Girol

Mimura

Drewes

et al. 2013

The Journal of Immunology

103

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“…do not become intracellular and do not have flagella, which makes it impossible for the amoebae to be recognized by TLR3 and TLR5. It has been demonstrated that double-stranded RNA and bacterial flagellin activate TLR3 and TLR5, respectively [42][43][44][45][46] . Attachment of Acanthamoeba to the corneal epithelial cells is the first step in pathogenesis of AK.…”

Section: Discussionmentioning

confidence: 99%

Identification of Acanthamoeba Membrane Protein That is Recognized by TLR4 on Corneal Epithelial Cells

Tripathi

Abdi

Alizadeh

2015

Receptor Clin Invest

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We have shown that Acanthamoeba spp. activate TLR4 on corneal epithelial cells and induce secretion of chemokines. However, the components of Acanthamoeba trophozoites that induce chemokines production remain unknown. We sought to identify the trophozoite molecules that interact with TLR4 on human corneal epithelial (HCE) cells and trigger IL-8 production. Acanthamoeba membrane protein (AcMP) was isolated by homogenization of trophozoites. The supernatants were collected, solubilized, and membrane fractions were separated by centrifugation using Mem-PER TM plus kit. To examine functional activity of AcMP, HCE and TLR4-expressing HEK293 cells were incubated with or without A. castellanii (1×10 5 cells/ml) and AcMP (10, 25, and 50 µg/ml) for 24 hours. AcMP was chromatographed by fast protein liquid chromatography (FPLC) and fractions were pooled into four peaks (AcMP-P1 -AcMP-P4). TLR4-ligand in AcMP-P1 -AcMP-P4 was determined by Western blotting. HEK293 and HCE cells were incubated with or without A. castellanii, lipopolysaccharide (LPS, 10 µg/ml), and AcMP-P1 -AcMP-P4 (20 µg/ml) for 24 hours. qRT-PCR and ELISA were used to examine the ability of AcMP-P1 -AcMP-P4 to stimulate IL-8 production in HEK293 and HCE cells. Inhibition of TLR4 involved preincubating HEK293 and HCE cells for 1 hour with neutralizing TLR4-antibody (10 µg/ml) or with the control antibody (10 µg/ml, goat serum) followed by incubation with or without A. castellanii, LPS, and AcMP-P2 for 24 hours. AcMP induced significant IL-8 production at doses of 10, 25, and 50 µg/ml in HEK293 cells while IL-8 mRNA expression and IL-8 secretion were significantly increased in HCE cells at the dose of 50 µg/ml. Treatments of HEK293 with FPLC chromatographed trophozoites' proteins, AcMP-P1 -AcMP-P4; only AcMP-P2 upregulated significant IL-8 production and mRNA expression. Western blotting of AcMP-P1 -AcMP-P4 showed TLR4-antigen in AcMP-P2 and was recognized an approximate 15-kDa protein band. Anti-TLR4 antibody attenuated IL-8 secretion that is stimulated by AcMP-P2 from HEK293 and HCE cells. These results suggest that A. castellanii trophozoites recognize TLR4 on HCE and HEK293 cells by an approximate 15-kDa molecular mass protein of AcMP and induce IL-8 secretion.

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“…Specifically, these adaptor molecules include myeloid differentiation primary-response protein 88 (MyD88, utilized by all TLRs except for TLR3), TIR-domain-containing adaptor protein (TI-RAP, also known as MyD88-adaptor-like protein (MAL), for TLR2 and TLR4), TIR domain-containing adaptor-inducing interferon-β (TRIF, also known as TIR-domain-containing adaptor molecule 1 (TICAM-1)), TRIF-related adaptor molecule (TRAM, also known as TIR-domain-containing adaptor molecule 2 (TICAM-2), for TLR3 and TLR4), and/or sterile and HEAT/armadillo (ARM) motif protein (SARM) (McGettrick and O'Neill, 2004). For more details of different TLR ligands and downstream factors, please refer the related reviews (Morrison, 2004;Chang et al, 2006;Herbst-Kralovetz and Pyles, 2006;Gay and Gangloff, 2007;Akira, 2010, 2011).…”

Section: Tlrsmentioning

confidence: 99%

Herpesviral infection and Toll-like receptor 2

Cai

Zheng

2012

Protein Cell

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In the last decade, substantial progress has been made in understanding the molecular mechanisms involved in the initial host responses to viral infections. Herpesviral infections can provoke an inflammatory cytokine response, however, the innate pathogen-sensing mechanisms that transduce the signal for this response are poorly understood. In recent years, it has become increasingly evident that the Toll-like receptors (TLRs), which are germline-encoded pattern recognition receptors (PRRs), function as potent sensors for infection. TLRs can induce the activation of the innate immunity by recruiting specific intracellular adaptor proteins to initiate signaling pathways, which then culminating in activation of the nuclear factor kappa B (NF-κB) and interferon-regulatory factors (IRFs) that control the transcription of genes encoding type I interferon (IFN I) and other inflammatory cytokines. Furthermore, activation of innate immunity is critical for mounting adaptive immune responses. In parallel, common mechanisms used by viruses to counteract TLR-mediated responses or to actively subvert these pathways that block recognition and signaling through TLRs for their own benefit are emerging. Recent findings have demonstrated that TLR2 plays a crucial role in initiating the inflammatory process, and surprisingly that the response TLR2 triggers might be overzealous in its attempt to counter the attack by the virus. In this review, we summarize and discuss the recent advances about the specific role of TLR2 in triggering inflammatory responses in herpesvirus infection and the consequences of the alarms raised in the host that they are assigned to protect.

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Toll-like receptors in ocular immunity and the immunopathogenesis of inflammatory eye disease

Cited by 156 publications

References 36 publications

Anti-Inflammatory Mechanisms of the Annexin A1 Protein and Its Mimetic Peptide Ac2-26 in Models of Ocular Inflammation In Vivo and In Vitro

Anti-Inflammatory Mechanisms of the Annexin A1 Protein and Its Mimetic Peptide Ac2-26 in Models of Ocular Inflammation In Vivo and In Vitro

Identification of Acanthamoeba Membrane Protein That is Recognized by TLR4 on Corneal Epithelial Cells

Herpesviral infection and Toll-like receptor 2

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