In Vitro Anti-inflammatory Effects of the Phenylbutyric Acid Metabolite Phenylacetyl Glutamine
| Autor: | Takuya Nishinakagawa, Mai Hazekawa, Tomoyo Kawakubo-Yasukochi, Kazuhiko Ono, Manabu Nakashima |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Pharmacology Lipopolysaccharide medicine.medical_treatment T cell Pharmaceutical Science General Medicine Molecular biology Proinflammatory cytokine Glutamine 03 medical and health sciences chemistry.chemical_compound Peritoneal cavity 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Cytokine chemistry Cell culture medicine Tumor necrosis factor alpha 030217 neurology & neurosurgery |
| Zdroj: | Biological and Pharmaceutical Bulletin. 41:961-966 |
| ISSN: | 1347-5215 0918-6158 |
| DOI: | 10.1248/bpb.b17-00799 |
| Popis: | Sodium 4-phenylbutyrate (PBA), which exerts a wide range of anti-inflammatory effects, is rapidly cleared from the body (approximately 98%) by urinary excretion by 24 h after oral treatment in humans. PBA was almost entirely excreted to urine as phenylacetyl glutamine (PAGln). However, no data describe the potential anti-inflammatory effects of PAGln. The purpose of this study was to evaluate the anti-inflammatory effects of PAGln on mouse spleen cells and peritoneal cavity cells, and explore the potential mechanism underlying this effect. PAGln was added to mouse spleen cell cultures stimulated by concanavalin A, or mouse peritoneal cavity cell cultures stimulated by lipopolysaccharide. After 72 h of culture, levels of inflammatory cytokines in culture supernatants were measured using a sandwich enzyme-linked immunosorbent assay system, and levels of inflammatory proteins were assessed by Western blotting. PAGln significantly inhibited inflammatory cytokine (interferon-γ, interleukin-6, and tumor necrosis factor-α) production, decrease of cell number in the spleen cell, and suppressed the expression of inflammatory proteins (nuclear factor κB, and inducible nitric oxide synthase). These results suggest that PAGln possesses anti-inflammatory activity via inhibition of T cell activation and Toll-like receptor 4 signaling. This study of the anti-inflammatory mechanism of PAGln provides useful information about its potential for therapeutic applications. |
| Databáze: | OpenAIRE |
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