PMID- 9602633
OWN - NLM
STAT- MEDLINE
DCOM- 19980602
LR  - 20190501
IS  - 0007-1161 (Print)
IS  - 1468-2079 (Electronic)
IS  - 0007-1161 (Linking)
VI  - 82
IP  - 3
DP  - 1998 Mar
TI  - Orbital fibroblast chemokine modulation: effects of dexamethasone and cyclosporin 
      A.
PG  - 318-22
AB  - 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.
FAU - Burnstine, M A
AU  - Burnstine MA
AD  - Department of Ophthalmology, W K Kellogg Eye Center, USA.
FAU - Elner, S G
AU  - Elner SG
FAU - Elner, V M
AU  - Elner VM
LA  - eng
GR  - EY-07003/EY/NEI NIH HHS/United States
GR  - EY-09441/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Br J Ophthalmol
JT  - The British journal of ophthalmology
JID - 0421041
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokines)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Interleukin-8)
RN  - 0 (RNA, Messenger)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - 83HN0GTJ6D (Cyclosporine)
SB  - IM
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Blotting, Northern
MH  - Cells, Cultured
MH  - Chemokine CCL2/analysis/antagonists & inhibitors
MH  - Chemokines/*metabolism
MH  - Cyclosporine/*pharmacology
MH  - Dexamethasone/*pharmacology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Eye Diseases/genetics/*metabolism
MH  - Fibroblasts/drug effects/metabolism
MH  - Humans
MH  - Immunosuppressive Agents/*pharmacology
MH  - Interleukin-8/analysis/antagonists & inhibitors
MH  - RNA, Messenger/analysis
PMC - PMC1722500
EDAT- 1998/05/29 00:00
MHDA- 1998/05/29 00:01
PMCR- 2001/03/01
CRDT- 1998/05/29 00:00
PHST- 1998/05/29 00:00 [pubmed]
PHST- 1998/05/29 00:01 [medline]
PHST- 1998/05/29 00:00 [entrez]
PHST- 2001/03/01 00:00 [pmc-release]
AID - 10.1136/bjo.82.3.318 [doi]
PST - ppublish
SO  - Br J Ophthalmol. 1998 Mar;82(3):318-22. doi: 10.1136/bjo.82.3.318.