Differential expression of chemokines by human retinal pigment epithelial cells infected with cytomegalovirus.
OBJECTIVE
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.
Momma
Yuko
Y
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA.
Nagineni
Chandrasekharam N
CN
Chin
Marian S
MS
Srinivasan
Kumar
K
Detrick
Barbara
B
Hooks
John J
JJ
D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism / Q000494:pharmacology; D018925:Chemokines / Q000235:genetics* / Q000378:metabolism; D003587:Cytomegalovirus / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000378:metabolism* / Q000821:virology*; D012333:RNA, Messenger / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D010948:Viral Plaque Assay; D014779:Virus Replication / Q000187:drug effects
D018932:Chemokine CCL2; D018925:Chemokines; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D007371:Interferon-gamma