Orbital fibroblast chemokine modulation: effects of dexamethasone and cyclosporin A.

Abstract

AIM:

Orbital inflammation is common, but the mechanisms underlying leucocytic infiltration of orbital tissue are poorly understood. Human orbital fibroblasts (OF) express chemokines, interleukin 8 (IL-8) and monocyte chemotactic protein 1 (MCP-1), when exposed to proinflammatory cytokines. The effect of dexamethasone (DEX) and cyclosporin A (CSA) on OF IL-8 and MCP-1 were examined.

METHODS:

Cultured human OF were incubated with recombinant interleukin 1 beta (rIL-1 beta; 0.2, 2.0, 20 ng/ml) alone or incubated with rIL-1 beta and DEX (10(-8), 10(-7), 10(-6) M) or CSA (3, 30, 300 ng/ml) for 24 hours. ELISA and northern blot analyses were performed to determine OF IL-8 and MCP-1 protein secretion and mRNA expression, respectively.

RESULTS:

OF lacked constitutive IL-8 or MCP-1 expression, but secreted significant amounts of these chemokines and expressed substantial steady state mRNA for both chemokines upon rIL-1 beta stimulation. DEX caused dose dependent inhibition of IL-1 induced IL-8 (p < 0.001) and MCP-1 (p < 0.05) secretion and mRNA expression at all concentrations of rIL-1 beta. CSA enhanced IL-1 induced OF IL-8 (p < 0.001) and suppressed rIL-1 beta induced OF MCP-1 (p < 0.05) secretion when lower doses of rIL-1 beta were used. These effects on secreted chemokines at different concentrations of rIL-1 beta and immunomodulating agents were corroborated by steady state OF IL-8 and MCP-1 mRNA expression.

CONCLUSIONS:

DEX is a potent inhibitor of OF IL-8 and MCP-1. In contrast, CSA enhances IL-1 induced OF IL-8 and suppresses OF MCP-1. These observations may explain the relative lack of CSA effectiveness in human orbital diseases that respond to corticosteroids.

• Authors: M A Burnstine, S G Elner, V M Elner
• Journal: The British journal of ophthalmology (Br J Ophthalmol) Vol. 82 Issue 3 Pg. 318-22 (Mar 1998) ISSN: 0007-1161 [Print] England
• PMID: 9602633 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anti-Inflammatory Agents
• Chemokine CCL2
• Chemokines
• Immunosuppressive Agents
• Interleukin-8
• RNA, Messenger
• Dexamethasone
• Cyclosporine

Topics

• Anti-Inflammatory Agents (pharmacology)
• Blotting, Northern
• Cells, Cultured
• Chemokine CCL2 (analysis, antagonists & inhibitors)
• Chemokines (metabolism)
• Cyclosporine (pharmacology)
• Dexamethasone (pharmacology)
• Enzyme-Linked Immunosorbent Assay
• Eye Diseases (genetics, metabolism)
• Fibroblasts (drug effects, metabolism)
• Humans
• Immunosuppressive Agents (pharmacology)
• Interleukin-8 (analysis, antagonists & inhibitors)
• RNA, Messenger (analysis)