Differential expression of chemokines by human retinal pigment epithelial cells infected with cytomegalovirus

Yuko Momma, Chandrasekharam N. Nagineni, Marian S. Chin, Kumar Srinivasan, Barbara Detrick, John J. Hooks

Research output: Contribution to journalArticle

Abstract

PURPOSE. To evaluate the effects of human cytomegalovirus (HCMV) infection on chemokine gene expression and secretion by human retinal pigment epithelial (HRPE) cell cultures. METHODS. HRPE cells were infected with HCMV (strain AD169) at an MOI of 5. Culture supernatants, collected at various postinoculation days, were used for the analyses of chemokines by ELISA. The steady state levels of chemokine and chemokine receptor mRNA were analyzed by RT-PCR. Effects of interferon and MCP-1 on HCMV replication in HRPE cells were evaluated by plaque assays. RESULTS. HRPE cells infected with HCMV exhibited characteristic cytopathic effects. The reduction in the levels of monocyte chemotactic protein (MCP)-1 and -3 mRNA in HCMV-infected HRPE cells was observed in comparison to uninfected HRPE cells. In contrast, HCMV infection enhanced IL-8 mRNA levels, whereas regulated on activation normal T-cell expressed and secreted (RANTES) mRNA was not detectable in either control or infected HRPE cells. A significant decrease in MCP-1 (P <0.01) and MCP-3 (P <0.05), but a significant increase in IL-8 (P <0.05), protein secretion was observed. Expression of the chemokine receptors CCR2, specific for MCP-1, and CXCR1 and CXCR2, specific for IL-8, were not altered by HCMV infection. Treatment of HRPE cultures with MCP-1 had no significant effect on HCMV replication in HRPE cells. CONCLUSIONS. HCMV infection in HRPE cells resulted in the modulation of MCP-1, MCP-3, and IL-8. Because chemokines facilitate the activation of leukocytes and their migration to the sites of inflammation, the modulation of chemokine production by the virus suggests a role for chemokines in immune evasion and/or immunopathogenesis of CMV retinitis.

Original languageEnglish (US)
Pages (from-to)2026-2033
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume44
Issue number5
DOIs
StatePublished - May 1 2003

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Retinal Pigments
Cytomegalovirus
Chemokines
Epithelial Cells
Chemokine CCL2
Chemokine CCL7
Cytomegalovirus Infections
Interleukin-8
Messenger RNA
Chemokine Receptors
Retinitis
Immune Evasion

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Differential expression of chemokines by human retinal pigment epithelial cells infected with cytomegalovirus. / Momma, Yuko; Nagineni, Chandrasekharam N.; Chin, Marian S.; Srinivasan, Kumar; Detrick, Barbara; Hooks, John J.

In: Investigative Ophthalmology and Visual Science, Vol. 44, No. 5, 01.05.2003, p. 2026-2033.

Research output: Contribution to journalArticle

Momma, Yuko ; Nagineni, Chandrasekharam N. ; Chin, Marian S. ; Srinivasan, Kumar ; Detrick, Barbara ; Hooks, John J. / Differential expression of chemokines by human retinal pigment epithelial cells infected with cytomegalovirus. In: Investigative Ophthalmology and Visual Science. 2003 ; Vol. 44, No. 5. pp. 2026-2033.
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abstract = "PURPOSE. To evaluate the effects of human cytomegalovirus (HCMV) infection on chemokine gene expression and secretion by human retinal pigment epithelial (HRPE) cell cultures. METHODS. HRPE cells were infected with HCMV (strain AD169) at an MOI of 5. Culture supernatants, collected at various postinoculation days, were used for the analyses of chemokines by ELISA. The steady state levels of chemokine and chemokine receptor mRNA were analyzed by RT-PCR. Effects of interferon and MCP-1 on HCMV replication in HRPE cells were evaluated by plaque assays. RESULTS. HRPE cells infected with HCMV exhibited characteristic cytopathic effects. The reduction in the levels of monocyte chemotactic protein (MCP)-1 and -3 mRNA in HCMV-infected HRPE cells was observed in comparison to uninfected HRPE cells. In contrast, HCMV infection enhanced IL-8 mRNA levels, whereas regulated on activation normal T-cell expressed and secreted (RANTES) mRNA was not detectable in either control or infected HRPE cells. A significant decrease in MCP-1 (P <0.01) and MCP-3 (P <0.05), but a significant increase in IL-8 (P <0.05), protein secretion was observed. Expression of the chemokine receptors CCR2, specific for MCP-1, and CXCR1 and CXCR2, specific for IL-8, were not altered by HCMV infection. Treatment of HRPE cultures with MCP-1 had no significant effect on HCMV replication in HRPE cells. CONCLUSIONS. HCMV infection in HRPE cells resulted in the modulation of MCP-1, MCP-3, and IL-8. Because chemokines facilitate the activation of leukocytes and their migration to the sites of inflammation, the modulation of chemokine production by the virus suggests a role for chemokines in immune evasion and/or immunopathogenesis of CMV retinitis.",
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T1 - Differential expression of chemokines by human retinal pigment epithelial cells infected with cytomegalovirus

AU - Momma, Yuko

AU - Nagineni, Chandrasekharam N.

AU - Chin, Marian S.

AU - Srinivasan, Kumar

AU - Detrick, Barbara

AU - Hooks, John J.

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N2 - PURPOSE. To evaluate the effects of human cytomegalovirus (HCMV) infection on chemokine gene expression and secretion by human retinal pigment epithelial (HRPE) cell cultures. METHODS. HRPE cells were infected with HCMV (strain AD169) at an MOI of 5. Culture supernatants, collected at various postinoculation days, were used for the analyses of chemokines by ELISA. The steady state levels of chemokine and chemokine receptor mRNA were analyzed by RT-PCR. Effects of interferon and MCP-1 on HCMV replication in HRPE cells were evaluated by plaque assays. RESULTS. HRPE cells infected with HCMV exhibited characteristic cytopathic effects. The reduction in the levels of monocyte chemotactic protein (MCP)-1 and -3 mRNA in HCMV-infected HRPE cells was observed in comparison to uninfected HRPE cells. In contrast, HCMV infection enhanced IL-8 mRNA levels, whereas regulated on activation normal T-cell expressed and secreted (RANTES) mRNA was not detectable in either control or infected HRPE cells. A significant decrease in MCP-1 (P <0.01) and MCP-3 (P <0.05), but a significant increase in IL-8 (P <0.05), protein secretion was observed. Expression of the chemokine receptors CCR2, specific for MCP-1, and CXCR1 and CXCR2, specific for IL-8, were not altered by HCMV infection. Treatment of HRPE cultures with MCP-1 had no significant effect on HCMV replication in HRPE cells. CONCLUSIONS. HCMV infection in HRPE cells resulted in the modulation of MCP-1, MCP-3, and IL-8. Because chemokines facilitate the activation of leukocytes and their migration to the sites of inflammation, the modulation of chemokine production by the virus suggests a role for chemokines in immune evasion and/or immunopathogenesis of CMV retinitis.

AB - PURPOSE. To evaluate the effects of human cytomegalovirus (HCMV) infection on chemokine gene expression and secretion by human retinal pigment epithelial (HRPE) cell cultures. METHODS. HRPE cells were infected with HCMV (strain AD169) at an MOI of 5. Culture supernatants, collected at various postinoculation days, were used for the analyses of chemokines by ELISA. The steady state levels of chemokine and chemokine receptor mRNA were analyzed by RT-PCR. Effects of interferon and MCP-1 on HCMV replication in HRPE cells were evaluated by plaque assays. RESULTS. HRPE cells infected with HCMV exhibited characteristic cytopathic effects. The reduction in the levels of monocyte chemotactic protein (MCP)-1 and -3 mRNA in HCMV-infected HRPE cells was observed in comparison to uninfected HRPE cells. In contrast, HCMV infection enhanced IL-8 mRNA levels, whereas regulated on activation normal T-cell expressed and secreted (RANTES) mRNA was not detectable in either control or infected HRPE cells. A significant decrease in MCP-1 (P <0.01) and MCP-3 (P <0.05), but a significant increase in IL-8 (P <0.05), protein secretion was observed. Expression of the chemokine receptors CCR2, specific for MCP-1, and CXCR1 and CXCR2, specific for IL-8, were not altered by HCMV infection. Treatment of HRPE cultures with MCP-1 had no significant effect on HCMV replication in HRPE cells. CONCLUSIONS. HCMV infection in HRPE cells resulted in the modulation of MCP-1, MCP-3, and IL-8. Because chemokines facilitate the activation of leukocytes and their migration to the sites of inflammation, the modulation of chemokine production by the virus suggests a role for chemokines in immune evasion and/or immunopathogenesis of CMV retinitis.

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