Differential Expression of Chemokines by Human Retinal Pigment Epithelial Cells Infected with Cytomegalovirus

Momma, Yuko; Nagineni, Chandrasekharam N.; Chin, Michael C.; Srinivasan, K.; Detrick, Barbara; Hooks, John J.

doi:10.1167/iovs.02-0980

Cited by 30 publications

(24 citation statements)

References 52 publications

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“…RPE cells were treated with IFN-␤, TNF-␣, IL-1␤, IFN-␥, alone or with the combinations of TNF ϩ IL-1␤; TNF ϩ IL-1␤ ϩ IFN-␥, or TNF-␣ ϩ IL-1␤ ϩ IFN-␥ ϩ IFN-␤. In earlier studies, we have shown that the combination of TNF-␣, IL-1␤, and IFN-␥ (cytomix) is a potent inducer of cytokines in RPE cells (17,25,30). As is seen in Fig.…”

Section: Production Of Cxcl9 By Rpe Cells and Inhibition By Ifn-␤mentioning

confidence: 68%

“…Moreover, IFN-␤ was not detected in cells treated with Poly d(I:C) (dsDNA), a negative control for poly(I:C) (dsRNA) (data not shown). However, these stimulants (LPS, cytomix) were capable of inducing sICAM-1 IL-8, MCP-1, MCP-3, RANTES, and TGF-␤ production in RPE cells (17,21,25).…”

Section: Kinetics Of Ifn-␤ Productionmentioning

confidence: 95%

“…In addition, numerous in vivo and in vitro studies have identified this cell as an ideal target for infectious agents such as, cytomegalovirus, Toxoplasma gondii, and coroanvirus (11)(12)(13)(14)(15). Furthermore, this cell is a rich source of cytokines, chemokines, and growth factors that may contribute to or limit pathologic processes (16,17). Studies have also shown that the RPE cell has a pivotal role in the immune system.…”

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confidence: 99%

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IFN-β Provides Immuno-Protection in the Retina by Inhibiting ICAM-1 and CXCL9 in Retinal Pigment Epithelial Cells

Hooks

Nagineni

Hooper

et al. 2008

The Journal of Immunology

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The retinal pigment epithelial (RPE) cell is a potent regulatory cell that facilitates normal physiologic processes and plays a critical role in a variety of retinal diseases. We evaluated IFN-β production in human RPE cells through TLR signaling and investigated the effects of IFN-β on RPE cells. RPE cells treated with poly(I:C) or infected with an RNA virus produce IFN-β. Kinetic studies revealed that IFN-β levels continue to increase over a 48-h period and this was associated with the up-regulation of IRF-7 gene expression, a known positive feedback molecule for IFN-β production. Microarray analysis revealed that in IFN-β treated cells, 480 genes of 22,283 genes were up or down-regulated by >2-fold. We hypothesize that IFN-β induction during TLR signaling in the retina is an immunosuppressive factor produced to limit immunopathologic damage. Cytokine activation of RPE cells results in the production of the chemokines, CXCL9 and CXCL10, and the adhesion molecule, ICAM-1. Pretreatment of RPE cells with IFN-β resulted in inhibition of ICAM-1 production and elimination of CXCL9 production. This treatment did not alter CXCL10 production. Anti-IFN-β Ab blocked the inhibitory action of IFN-β. Real time PCR analysis revealed that IFN-β treatment inhibited gene expression of sICAM-1 and CXCL9. The results indicate a critical role for RPE cell derived IFN-β in the down-regulation of CXCL9 and ICAM-1 expression in the retina and suggest that the inhibition of CXCL9 is an immuno-suppressive mechanism that protects the retina from excessive inflammation.

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Section: Production Of Cxcl9 By Rpe Cells and Inhibition By Ifn-␤mentioning

confidence: 68%

Section: Kinetics Of Ifn-␤ Productionmentioning

confidence: 95%

mentioning

confidence: 99%

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IFN-β Provides Immuno-Protection in the Retina by Inhibiting ICAM-1 and CXCL9 in Retinal Pigment Epithelial Cells

Hooks

Nagineni

Hooper

et al. 2008

The Journal of Immunology

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“…The RPE acts as a blood retinal barrier and regulates, a) transport of fluids, nutrients and wastes from the choroid to the retina and vice versa b) engulfment and digestion digest photoreceptor outer segments c) secretion of extracellular matrix materials for retinal adhesion and maintenance of the integrity of Bruch's membrane [18,19]. RPE secretes a number of growth factors, cytokines and chemokines and participates in the regulation of physiology and patho-biology of neuroretina and choroid [20][21][22][23][24][25][26][27][28].…”

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confidence: 99%

Inflammatory Cytokines Induce Expression of Chemokines by Human Retinal Cells: Role in Chemokine Receptor Mediated Age-related Macular Degeneration

et al. 2015

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“…Isolated rat RPE cells and human RPE cells have demonstrated antigen-presenting activity (46) and Toll-like receptor (TLR1 to -7, -9, and -10) expression (34), respectively. Inflammatory conditions also stimulated cytokine expression by human RPE cells, including lipopolysaccharide-induced COX-2 (18), interleukin-1␣ (IL-1␣)-induced IL-1␤ (48), and human cytomegalovirus-induced IL-8 (41). However, the potential role of RPE cells in inflammation during endophthalmitis has not been examined.…”

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confidence: 99%

Bacillus cereusInduces Permeability of an In Vitro Blood-Retina Barrier

Moyer¹,

Ramadan

Thurman³

et al. 2008

Infect Immun

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Most Bacillus cereus toxin production is controlled by the quorum-sensing-dependent, pleiotropic global regulator plcR, which contributes to the organism's virulence in the eye. The purpose of this study was to analyze the effects of B. cereus infection and plcR-regulated toxins on the barrier function of retinal pigment epithelium (RPE) cells, the primary cells of the blood-retina barrier. Human ARPE-19 cells were apically inoculated with wild-type or quorum-sensing-deficient B. cereus, and cytotoxicity was analyzed. plcR-regulated toxins were not required for B. cereus-induced RPE cytotoxicity, but these toxins did increase the rate of cell death, primarily by necrosis. B. cereus infection of polarized RPE cell monolayers resulted in increased barrier permeability, independent of plcR-regulated toxins. Loss of both occludin and ZO-1 expression occurred by 8 h postinfection, but alterations in tight junctions appeared to precede cytotoxicity. Of the several proinflammatory cytokines analyzed, only interleukin-6 was produced in response to B. cereus infection. These results demonstrate the deleterious effects of B. cereus infection on RPE barrier function and suggest that plcRregulated toxins may not contribute significantly to RPE barrier permeability during infection.

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Differential Expression of Chemokines by Human Retinal Pigment Epithelial Cells Infected with Cytomegalovirus

Cited by 30 publications

References 52 publications

IFN-β Provides Immuno-Protection in the Retina by Inhibiting ICAM-1 and CXCL9 in Retinal Pigment Epithelial Cells

IFN-β Provides Immuno-Protection in the Retina by Inhibiting ICAM-1 and CXCL9 in Retinal Pigment Epithelial Cells

Inflammatory Cytokines Induce Expression of Chemokines by Human Retinal Cells: Role in Chemokine Receptor Mediated Age-related Macular Degeneration

Bacillus cereusInduces Permeability of an In Vitro Blood-Retina Barrier

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