Constitutive and Inflammatory Mediator-Regulated Fractalkine Expression in Human Ocular Tissues and Cultured Cells

Silverman, Matthew D.; Zamora, David O.; Pan, Yuzhen; Texeira, Paul V.; Baek, Seung Hee; Planck, Stephen R.

doi:10.1167/iovs.02-0233

Cited by 78 publications

(66 citation statements)

References 40 publications

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“…CCL5 is also chemotactic for Th1 but not Th2 cells (49). Interestingly, negative regulation of CX3CL1 by IL-17 in ocular epithelial cells has also been reported (25). Like CXCL10, CXCL11, and CCL5, CX3CL1 is selectively chemotactic for Th1 cells and acts as an amplifier of polarized Th1 responses (50).…”

Section: Discussionmentioning

confidence: 95%

“…Whereas TNF-␣ induces transcription of the genes for CXCL1 and CXCL8 by activating the NF-B signaling pathway, IL-17 appears to act mainly by stabilizing their mRNAs (19,20). Intriguingly, however, IL-17 negatively regulates TNF-␣-elicited production of other chemokines including CCL5 (RANTES) (23,24), CX3CL1 (fractalkine) (25), and CCL27 (cutaneous T cell-attracting chemokine or CTACK) (26). Moreover, in a mouse model of allergic asthma, IL-17 functions as a negative regulator by repressing expression of the eosinophil chemokine CCL11 (eotaxin) and Th2 chemokine CCL17 (thymus-and activation-regulated chemokine or TARC) (27).…”

Section: Differential Regulation Of Chemokines By Il-17 In Colonicmentioning

confidence: 99%

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Differential Regulation of Chemokines by IL-17 in Colonic Epithelial Cells

Lee

Wang

Kattah³

et al. 2008

The Journal of Immunology

115

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The IL-23/IL-17 pathway plays an important role in chronic inflammatory diseases, including inflammatory bowel disease. In inflammatory bowel disease, intestinal epithelial cells are an important source of chemokines that recruit inflammatory cells. We examined the effect of IL-17 on chemokine expression of HT-29 colonic epithelial cells. IL-17 strongly repressed TNF-α-stimulated expression of CXCL10, CXCL11, and CCL5, but synergized with TNF-α for induction of CXCL8, CXCL1, and CCL20 mRNAs. For CXCL10, IL-17 strongly inhibited promoter activity but had no effect on mRNA stability. In contrast, for CXCL8, IL-17 slightly decreased promoter activity but stabilized its normally unstable mRNA, leading to a net increase in steady-state mRNA abundance. IL-17 synergized with TNF-α in transactivating the epidermal growth factor receptor (EGFR) and in activating ERK and p38 MAPK. The p38 and ERK pathway inhibitors SB203580 and U0126 reversed the repressive effect of IL-17 on CXCL10 mRNA abundance and promoter activity and also reversed the inductive effect of IL-17 on CXCL8 mRNA, indicating that MAPK signaling mediates both the transcriptional repression of CXCL10 and the stabilization of CXCL8 mRNA by IL-17. The EGFR kinase inhibitor AG1478 partially reversed the effects of IL-17 on CXCL8 and CXCL10 mRNA, demonstrating a role for EGFR in downstream IL-17 signaling. The overall results indicate a positive effect of IL-17 on chemokines that recruit neutrophils (CXCL8 and CXCL1), and Th17 cells (CCL20). In contrast, IL-17 represses expression of CXCL10, CXCL11, and CCR5, three chemokines that selectively recruit Th1 but not other effector T cells.

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Section: Discussionmentioning

confidence: 95%

Section: Differential Regulation Of Chemokines By Il-17 In Colonicmentioning

confidence: 99%

Differential Regulation of Chemokines by IL-17 in Colonic Epithelial Cells

Lee

Wang

Kattah³

et al. 2008

The Journal of Immunology

115

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“…Our data are consistent with the infiltration of the subretinal space by activated MCs previously described in AMD (15) and indicate that a specific inflammatory environment characterized by production of specific cytokines and chemokines may determine particular pathological conditions. Cells of the CNS and of the retina express CX3CL1 abundantly (26,27). On the other hand, RPE cells under oxidative stress express other monocyte chemoattractant chemokines such as CCL2 (28), which may be responsible for the recruitment of MCs in the subretinal space.…”

Section: Discussionmentioning

confidence: 99%

CX3CR1-dependent subretinal microglia cell accumulation is associated with cardinal features of age-related macular degeneration

Combadière¹,

Feumi²,

Raoul³

et al. 2007

J. Clin. Invest.

504

653

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The role of retinal microglial cells (MCs) in age-related macular degeneration (AMD) is unclear. Here we demonstrated that all retinal MCs express CX3C chemokine receptor 1 (CX3CR1) and that homozygosity for the CX3CR1 M280 allele, which is associated with impaired cell migration, increases the risk of AMD. In humans with AMD, MCs accumulated in the subretinal space at sites of retinal degeneration and choroidal neovascularization (CNV). In CX3CR1-deficient mice, MCs accumulated subretinally with age and albino background and after laser impact preceding retinal degeneration. Raising the albino mice in the dark prevented both events. The appearance of lipid-bloated subretinal MCs was drusen-like on funduscopy of senescent mice, and CX3CR1-dependent MC accumulation was associated with an exacerbation of experimental CNV. These results show that CX3CR1-dependent accumulation of subretinal MCs evokes cardinal features of AMD. These findings reveal what we believe to be a novel pathogenic process with important implications for the development of new therapies for AMD.

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“…It is thought to play an important role in regulating leukocyte efflux in inflammatory eye diseases, such as anterior uveitis and retinochoroiditis. 77 Fractalkine upregulation prior to disease onset in experimental autoimmune uveitis has also been demonstrated. 78 As yet, only the chemokines IL-8, MIP-1β and MCP-1 have been investigated in the aqueous humor in patients with acute anterior uveitis, 13,79 and CCL2 (MCP-1), CCL5 (RANTES), CCL11 (Eotaxin), TGF-β2 and CXCL12 (SDF-1) have been investigated in patients with anterior uveitis.…”

Section: Chemokines In Experimental Uveitismentioning

confidence: 98%

Cytokines and Chemokines in Uveitis - Is there a Correlation with Clinical Phenotype?

Ooi¹,

Galatowicz²,

Calder³

et al. 2006

Clinical Medicine & Research

130

118

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Constitutive and Inflammatory Mediator-Regulated Fractalkine Expression in Human Ocular Tissues and Cultured Cells

Abstract: FKN is expressed in various ocular tissues and cells. Inflammatory mediator modulation of ocular FKN expression suggests that this adhesive chemokine may play important roles in regulating leukocyte efflux in inflammatory eye diseases, such as anterior uveitis and retinochoroiditis.

Cited by 78 publications

References 40 publications

Differential Regulation of Chemokines by IL-17 in Colonic Epithelial Cells

Differential Regulation of Chemokines by IL-17 in Colonic Epithelial Cells

CX3CR1-dependent subretinal microglia cell accumulation is associated with cardinal features of age-related macular degeneration

Cytokines and Chemokines in Uveitis - Is there a Correlation with Clinical Phenotype?

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