Inhibition of inflammatory cytokine production in human corneal cells by dexamethasone, but not cyclosporin.
OBJECTIVE
To evaluate the modulatory effects of anti-inflammatory agents, dexamethasone (Dex) and cyclosporin A (CsA), on the production of cytokines and chemokines by human corneal cells in vitro following stimulation by the pro-inflammatory cytokine after interleukin 1beta (IL-1beta).


METHODS
A human corneal epithelial (HCE) cell line and human corneal fibroblasts (HCFs) were stimulated in culture with IL-1beta and treated with Dex or CsA. The gene expression for selected cytokines and chemokines was determined by reverse transcriptase-polymerase chain reaction (RT-PCR). The secretion of cytokines and chemokines was measured by enzyme-linked immunosorbent assay.


RESULTS
IL-1beta enhanced the mRNA and/or protein levels of granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-8, and monocyte chemotactic protein (MCP)-1 in HCE and IL-6, IL-8, MCP-3, and regulated on T-cell activation expressed secreted (RANTES) in HCFs. Treatment with CsA did not inhibit cytokine production in either HCE or HCFs. In contrast, Dex treatment inhibited the IL-1beta-induced production of GM-CSF, IL-6, IL-8, MCP-3, and RANTES, but not MCP-1.


CONCLUSIONS
These results show that Dex, but not CsA, has direct immunosuppressive effects on the resident corneal cells, HCE and HCFs. This suggests that the clinically observed immunosuppressive effects of topical CsA are mediated primarily through the immune cells.
Djalilian
Ali R
AR
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD, USA. adjalili@uic.edu
Nagineni
Chandrasekharam N
CN
Mahesh
Sankanaranayana P
SP
Smith
Janine A
JA
Nussenblatt
Robert B
RB
Hooks
John J
JJ
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D018929:Cell Culture Techniques; D018932:Chemokine CCL2 / Q000235:genetics; D018946:Chemokine CCL5 / Q000235:genetics; D054410:Chemokine CCL7; D003319:Corneal Stroma / Q000166:cytology; D016572:Cyclosporine / Q000494:pharmacology*; D016207:Cytokines / Q000235:genetics*; D003907:Dexamethasone / Q000494:pharmacology*; D019573:Epithelium, Corneal / Q000187:drug effects* / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000494:pharmacology; D015850:Interleukin-6 / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics; D018945:Monocyte Chemoattractant Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000893:Anti-Inflammatory Agents; C111835:CCL2 protein, human; C515450:CCL7 protein, human; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D054410:Chemokine CCL7; D016207:Cytokines; D007166:Immunosuppressive Agents; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D018945:Monocyte Chemoattractant Proteins; D012333:RNA, Messenger; D003907:Dexamethasone; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D016572:Cyclosporine