Dietary Glycine Prevents Peptidoglycan Polysaccharide-Induced Reactive Arthritis in the Rat: Role for Glycine-Gated Chloride Channel
Autor: | Heather M. Pink, Blair U. Bradford, Thomas A. Brodie, Michael D. Wheeler, Ronald G. Thurman, Xiangli Li, Stephen A. Stimpson, John H. Schwab |
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Rok vydání: | 2001 |
Předmět: |
Male
medicine.medical_specialty medicine.medical_treatment Immunology Glycine Arthritis Peptidoglycan Biology Arthritis Reactive Microbiology Eating chemistry.chemical_compound Chloride Channels Superoxides Internal medicine medicine Animals Glycine receptor Calcium metabolism Host Response and Inflammation Macrophages Body Weight Polysaccharides Bacterial NF-kappa B Strychnine medicine.disease Rats Infectious Diseases Endocrinology Cytokine chemistry Rats Inbred Lew Dietary Supplements Chloride channel Calcium Parasitology Tumor necrosis factor alpha Ion Channel Gating Ankle Joint Spleen |
Zdroj: | Infection and Immunity. 69:5883-5891 |
ISSN: | 1098-5522 0019-9567 |
DOI: | 10.1128/iai.69.9.5883-5891.2001 |
Popis: | Peptidoglycan polysaccharide (PG-PS) is a primary structural component of bacterial cell walls and causes rheumatoid-like arthritis in rats. Recently, glycine has been shown to be a potential immunomodulator; therefore, the purpose of this study was to determine if glycine would be protective in a PG-PS model of arthritis in vivo. In rats injected with PG-PS intra-articularly, ankle swelling increased 21% in 24 to 48 h and recovered in about 2 weeks. Three days prior to reactivation with PG-PS given intravenously (i.v.), rats were divided into two groups and fed a glycine-containing or nitrogen-balanced control diet. After i.v. PG-PS treatment joint swelling increased 2.1 ± 0.3 mm in controls but only 1.0 ± 0.2 mm in rats fed glycine. Infiltration of inflammatory cells, edema, and synovial hyperplasia in the joint were significantly attenuated by dietary glycine. Tumor necrosis factor alpha (TNF-α) mRNA was detected in ankle homogenates from rats fed the control diet but not in ankles from rats fed glycine. Moreover, intracellular calcium was increased significantly in splenic macrophages treated with PG-PS; however, glycine blunted the increase about 50%. The inhibitory effect of glycine was reversed by low concentrations of strychnine or chloride-free buffer, and it increased radiolabeled chloride influx nearly fourfold, an effect also inhibited by strychnine. In isolated splenic macrophages, glycine blunted translocation of the p65 subunit of NF-κB into the nucleus, superoxide generation, and TNF-α production caused by PG-PS. Further, mRNA for the beta subunit of the glycine receptor was detected in splenic macrophages. This work supports the hypothesis that glycine prevents reactive arthritis by blunting cytokine release from macrophages by increasing chloride influx via a glycine-gated chloride channel. |
Databáze: | OpenAIRE |
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