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Inhibitory effects of glucosamine on endotoxin-induced uveitis in Lewis rats.
Invest Ophthalmol Vis Sci 2008; 49(12):5441-9IO

Abstract

PURPOSE

Glucosamine sulfate (GS) is a naturally occurring sugar that exerts immunosuppressive effects in vitro and in vivo. The authors investigated whether GS modulates the inflammatory reaction in endotoxin-induced uveitis (EIU) of rats and the mechanisms by which it exerts its effects.

METHODS

Two-hundred micrograms of lipopolysaccharide (LPS) was injected subcutaneously into Lewis rats to induce EIU. Doses of GS (10, 100, or 1000 mg/kg) were divided into three aliquots and administered intraperitoneally 30 minutes before LPS injection, concurrently with LPS injection, and 30 minutes after LPS injection. Twenty-four hours after LPS injection, aqueous humor was collected for cell counting and measurement of protein concentration. Immunohistochemical staining of the iris-ciliary body was performed to evaluate the effects of GS on intercellular adhesion molecule (ICAM)-1 and nuclear factor (NF)-kappaB activation and to demonstrate macrophage infiltration. The effects of various doses of GS pretreatment were also examined using a mouse macrophage cell line (RAW264.7 cells) and LPS stimulation. Levels of prostaglandin (PG)-E2 and nitric oxide (NO) were determined. Expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 were measured using Western blot analysis. The effect of GS on LPS-induced NF-kappaB activation in RAW cells was also examined.

RESULTS

Cell counting and analysis of protein concentration in aqueous humor revealed that GS suppressed EIU in rats treated with a high dose of GS (1000 mg/kg). Immunohistochemistry showed that treatment with GS reduced ICAM-1 expression and suppressed activation of NF-kappaB in the iris-ciliary body. The main inflammatory cells in the iris-ciliary body during EIU were macrophages. In LPS-stimulated macrophage RAW cell culture, GS inhibited the production of NO and PG-E2, the expression of iNOS and COX-2, and the activation of NF-kappaB.

CONCLUSIONS

GS suppresses EIU in rats by blockading the NF-kappaB-dependent signaling pathway and the subsequent production of ICAM-1 and proinflammatory mediators. This study has extended the authors' previous observation that GS is a potentially important compound for reducing ICAM-1-mediated inflammatory effects in the eye.

Authors+Show Affiliations

Department of Ophthalmology, Tri-Service General Hospital, Taipei, Taiwan, Republic of China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18719082

Citation

Chang, Yun-Hsiang, et al. "Inhibitory Effects of Glucosamine On Endotoxin-induced Uveitis in Lewis Rats." Investigative Ophthalmology & Visual Science, vol. 49, no. 12, 2008, pp. 5441-9.
Chang YH, Horng CT, Chen YH, et al. Inhibitory effects of glucosamine on endotoxin-induced uveitis in Lewis rats. Invest Ophthalmol Vis Sci. 2008;49(12):5441-9.
Chang, Y. H., Horng, C. T., Chen, Y. H., Chen, P. L., Chen, C. L., Liang, C. M., ... Chen, J. T. (2008). Inhibitory effects of glucosamine on endotoxin-induced uveitis in Lewis rats. Investigative Ophthalmology & Visual Science, 49(12), pp. 5441-9. doi:10.1167/iovs.08-1784.
Chang YH, et al. Inhibitory Effects of Glucosamine On Endotoxin-induced Uveitis in Lewis Rats. Invest Ophthalmol Vis Sci. 2008;49(12):5441-9. PubMed PMID: 18719082.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibitory effects of glucosamine on endotoxin-induced uveitis in Lewis rats. AU - Chang,Yun-Hsiang, AU - Horng,Chi-Ting, AU - Chen,Yi-Hao, AU - Chen,Po-Liang, AU - Chen,Ching-Long, AU - Liang,Chang-Min, AU - Chien,Ming-Wei, AU - Chen,Jiann-Torng, Y1 - 2008/08/21/ PY - 2008/8/23/pubmed PY - 2008/12/23/medline PY - 2008/8/23/entrez SP - 5441 EP - 9 JF - Investigative ophthalmology & visual science JO - Invest. Ophthalmol. Vis. Sci. VL - 49 IS - 12 N2 - PURPOSE: Glucosamine sulfate (GS) is a naturally occurring sugar that exerts immunosuppressive effects in vitro and in vivo. The authors investigated whether GS modulates the inflammatory reaction in endotoxin-induced uveitis (EIU) of rats and the mechanisms by which it exerts its effects. METHODS: Two-hundred micrograms of lipopolysaccharide (LPS) was injected subcutaneously into Lewis rats to induce EIU. Doses of GS (10, 100, or 1000 mg/kg) were divided into three aliquots and administered intraperitoneally 30 minutes before LPS injection, concurrently with LPS injection, and 30 minutes after LPS injection. Twenty-four hours after LPS injection, aqueous humor was collected for cell counting and measurement of protein concentration. Immunohistochemical staining of the iris-ciliary body was performed to evaluate the effects of GS on intercellular adhesion molecule (ICAM)-1 and nuclear factor (NF)-kappaB activation and to demonstrate macrophage infiltration. The effects of various doses of GS pretreatment were also examined using a mouse macrophage cell line (RAW264.7 cells) and LPS stimulation. Levels of prostaglandin (PG)-E2 and nitric oxide (NO) were determined. Expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 were measured using Western blot analysis. The effect of GS on LPS-induced NF-kappaB activation in RAW cells was also examined. RESULTS: Cell counting and analysis of protein concentration in aqueous humor revealed that GS suppressed EIU in rats treated with a high dose of GS (1000 mg/kg). Immunohistochemistry showed that treatment with GS reduced ICAM-1 expression and suppressed activation of NF-kappaB in the iris-ciliary body. The main inflammatory cells in the iris-ciliary body during EIU were macrophages. In LPS-stimulated macrophage RAW cell culture, GS inhibited the production of NO and PG-E2, the expression of iNOS and COX-2, and the activation of NF-kappaB. CONCLUSIONS: GS suppresses EIU in rats by blockading the NF-kappaB-dependent signaling pathway and the subsequent production of ICAM-1 and proinflammatory mediators. This study has extended the authors' previous observation that GS is a potentially important compound for reducing ICAM-1-mediated inflammatory effects in the eye. SN - 1552-5783 UR - https://www.unboundmedicine.com/medline/citation/18719082/Inhibitory_effects_of_glucosamine_on_endotoxin_induced_uveitis_in_Lewis_rats_ L2 - http://iovs.arvojournals.org/article.aspx?doi=10.1167/iovs.08-1784 DB - PRIME DP - Unbound Medicine ER -