The Effect of Denatured Flagellin on Toll-Like Receptor-5 (TLR-5) in Mice
| Autor: | Nayla S. Al-Akl, Alexander M. Abdelnoor, Soha Mcheik |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Salmonella typhimurium
0301 basic medicine Protein Denaturation Endocrinology Diabetes and Metabolism medicine.disease_cause Microbiology 03 medical and health sciences In vivo medicine Animals Immunology and Allergy Pseudomonas Infections Cells Cultured Mice Inbred BALB C Toll-like receptor biology Tumor Necrosis Factor-alpha Pseudomonas aeruginosa Chemistry Interleukin-12 In vitro Disease Models Animal Toll-Like Receptor 5 030104 developmental biology TLR5 Host-Pathogen Interactions Leukocytes Mononuclear biology.protein Interleukin 12 Female Tumor necrosis factor alpha Flagellin Protein Binding Signal Transduction |
| Zdroj: | Endocrine, Metabolic & Immune Disorders - Drug Targets. 18:412-416 |
| ISSN: | 1871-5303 |
| Popis: | Background Previous studies have demonstrated that flagellin, a component of bacterial flagella, engages Toll-Like receptor 5 (TLR-5) causing the activation of the Myeloid Differentiation Factor-88 (MYD-88) pathway that leads to the production of pro-inflammatory cytokines including Tumor Necrosis Factor-alpha (TNF-α) and Interleukin-12 (IL-12). In physiological levels, cytokines can aid in protection against infectious agents. However, excessive production of cytokines can lead to septic shock during sepsis. Objective In this study, we aimed at investigating the effect of denatured flagellin on hindering the effects induced by intact flagellin or flagellated Pseudomonas aeruginosa on the Toll-Like Receptor-5 (TLR-5) in mice. Methods Mouse mononuclear cells (MNCs) were cultured with intact flagellin, heat-denatured flagellin, TLR-5 antagonist, Pseudomonas aeruginosa, and TLR-4 antagonist each alone or in combinations. Supernatants were collected at 4 hours post incubation to assess the levels of IL-12 and TNF-α by Enzyme-Linked ImmunoAssay (ELISA). Furthermore, groups of BALB/c mice were injected intraperitoneally (IP) with Pseudomonas aeruginosa, LPS-RS, intact flagellin, and denatured flagellin, each alone or in different combinations. Serum levels of IL-12 and TNF-α were measured at 2, 4, and 6 hours post injections of Pseudomonas aeruginosa or intact flagellin. Results Pretreatment with denatured flagellin significantly reduced the amount of TNF-α and IL-12 produced both in vitro and in vivo by intact flagellin or Pseudomonas aeruginosa. Conclusion Denatured flagellin suppressed the production of the pro-inflammatory cytokines induced by intact flagellin or Pseudomonas aeruginosa both in vitro and in vivo, probably by blocking TLR5. Denatured flagellin might be considered as an anti-septic shock agent. |
| Databáze: | OpenAIRE |
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