Document Detail

Rabbit pigmented ciliary epithelium produces interleukin-6 in response to inflammatory cytokines.
MedLine Citation:
PMID:  10712813     Owner:  NLM     Status:  MEDLINE    
Interleukin-6 is a multifunctional cytokine that is found in high concentrations in intraocular fluids during the uveitic response. Although monocytic cells are a major source of interleukin-6, resident intraocular cells may also contribute to its accumulation in intraocular fluids during uveitis. The purpose of this study was to determine whether interleukin-6 is produced by pigmented ciliary epithelial cells and whether agents known to stimulate interleukin-6 production, such as interleukin-1beta, tumor necrosis factor-alpha, bacterial endotoxin, and stimulators of the adenylyl cyclase/adenosine 3',5'-cyclic monophosphate system, increase interleukin-6 production by these cells. Primary and first-passage cultures of nontransformed rabbit pigmented ciliary epithelial cells were incubated with the test agents for varying periods of time in serum-free medium and interleukin-6 levels in the cell-conditioned medium were measured by bioassay.Little, if any interleukin-6 was released from pigmented ciliary epithelial cells incubated for up to 18 hr in serum-free medium. Interleukin-1betastimulated interleukin-6 release in a time- and concentration-dependent manner. Tumor necrosis factor-alpha, although ineffective alone, increased interleukin-1beta-induced interleukin-6 release in a concentration-dependent manner when co-incubated with interleukin-1betafor 18 hr. However, tumor necrosis factor-alphadid not enhance interleukin-1beta-induced interleukin-6 release if co-incubated with interleukin-1betafor a shorter time (6 hr). A 6 hr exposure to bacterial endotoxin did not stimulate interleukin-6 release from pigmented ciliary epithelial cells. Co-incubation of pigmented ciliary epithelial cells with interleukin-1betaand agents that stimulate the adenyl cyclase/adenosine 3',5'-cyclic monophosphate system through cell surface G-protein transduced receptors, i.e. isoproterenol, vasoactive intestinal peptide or prostaglandin E(2), significantly enhanced the ability of interleukin-1betato stimulate interleukin-6 release. However, neither the adenyl cyclase activator, forskolin or the adenosine 3', 5'-cyclic monophosphate-mimetic, dibutyryl 3',5'-cyclic monophosphate enhanced interleukin-1beta-induced release of interleukin-6. These results indicate that the pigmented ciliary epithelium is one potential source of interleukin-6 and may contribute to the elevation in intraocular fluid interleukin-6 levels observed during various intraocular inflammatory episodes. Although agents that activate the adenyl cyclase/adenosine 3', 5'-cyclic monophosphate system through cell surface G-protein transduced receptors increased interleukin-1beta-induced release of interleukin-6, the ineffectiveness of forskolin and dibutryl 3', 5'-cyclic monophosphate suggest that simply increasing intracellular 3',5'-cyclic monophosphate is not sufficient to augment interleukin-1beta-induced release of interleukin-6. The significance of interleukin-6 in the intraocular inflammatory response is discussed in terms of its proposed role in an endogenous antiinflammatory system acting through induction of interleukin-1 receptor antagonist, soluble tumor necrosis factor receptor, acute-phase proteins and corticosteroids.
L N Fleisher; M C McGAHAN; J B Ferrell
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Experimental eye research     Volume:  70     ISSN:  0014-4835     ISO Abbreviation:  Exp. Eye Res.     Publication Date:  2000 Mar 
Date Detail:
Created Date:  2000-04-17     Completed Date:  2000-04-17     Revised Date:  2009-11-03    
Medline Journal Info:
Nlm Unique ID:  0370707     Medline TA:  Exp Eye Res     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  271-9     Citation Subset:  IM    
Copyright Information:
Copyright 2000 Academic Press.
Department of Anatomy, Physiological Sciences and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA.
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MeSH Terms
Cell Culture Techniques
Ciliary Body / immunology*,  metabolism
Cyclic AMP / metabolism
Cytokines / immunology*
Endotoxins / immunology
Interleukin-1 / immunology
Interleukin-6 / biosynthesis*
Pigment Epithelium of Eye / immunology*,  metabolism
Tumor Necrosis Factor-alpha / immunology
Reg. No./Substance:
0/Cytokines; 0/Endotoxins; 0/Interleukin-1; 0/Interleukin-6; 0/Tumor Necrosis Factor-alpha; 60-92-4/Cyclic AMP

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