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J Ocul Pharmacol Ther. 2006 Dec;22(6):402-16.

Glucosamine sulfate inhibits proinflammatory cytokine-induced icam-1 production in human conjunctival cells in vitro.

Author information

1
Department of Ophthalmology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China. jt66chen@ms32.hinet.net

Abstract

PURPOSE:

We investigated whether glucosamine sulfate modulates the production of ICAM-1 induced by proinflammatory cytokines and whether glucosamine sulfate inhibits leukocyte adhesion to a monolayer of human conjunctival epithelial cells stimulated with proinflammatory cytokines.

METHODS:

We used flow cytometry and either primary cultured human conjunctival cells or the Chang conjunctival cell model to determine the effects of glucosamine sulfate on the production of ICAM-1 in response to tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-1beta, IL-6, TNF-alpha plus IFN-gamma, or TNF-alpha plus IL-1beta. The effects of glucosamine sulfate on the expression of the ICAM-1 gene, upregulated by various cytokines, were determined by semiquantitative reverse transcription-polymerase chain reaction. The activation and nuclear translocation of the nuclear factors NF-kappaB and STAT1 were evaluated by the transient transfection of reporter gene systems and immunocytochemistry. The influence of glucosamine-sulfate-modulated ICAM-1 on neutrophil adhesion was demonstrated in a model that measures the adherence of conjunctival cells and neutrophils.

RESULTS:

TNF-alpha, IFN-gamma, and IL-1beta significantly increased the production of ICAM-1 by both primary cultured human conjunctival cells and Chang conjunctival cells. Glucosamine sulfate effectively downregulated the production of ICAM-1 induced by TNF-alpha, IFN-gamma, IL-1beta, TNF-alpha plus IFN-gamma, or TNF-alpha plus IL-1beta. This downregulation occurred through the interferon-stimulated response element, IFN-gamma activation sequence, and binding sequence of NF-kappaB at the mRNA and protein levels. Glucosamine sulfate further inhibited the nuclear translocation of p65 protein in TNF-alpha- and IL-1beta-stimulated Chang conjunctival cells and phosphorylated STAT1 in IFN-gamma-stimulated Chang conjunctival cells. Glucosamine sulfate also significantly reduced the number of neutrophils adhering to a conjunctival monolayer in response to TNF-alpha, IFN-gamma, or IL-1beta.

CONCLUSIONS:

Our results suggest that glucosamine sulfate inhibits ICAM-1 production in conjunctival epithelial cells in vitro. Therefore, glucosamine sulfate might be valuable in the treatment of inflammatory ocular-surface conditions.

PMID:
17238806
DOI:
10.1089/jop.2006.22.402
[Indexed for MEDLINE]

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