The Effect of Denatured Flagellin on Toll-Like Receptor-5 (TLR-5) in Mice

Title:The Effect of Denatured Flagellin on Toll-Like Receptor-5 (TLR-5) in Mice

Volume: 18 Issue: 4

Author(s): Soha Mcheik, Nayla S. Al-Akl and Alexander M. Abdelnoor*

Affiliation:

• Department of Experimental Pathology, Immunology and Microbiology, Faculty of Medicine, American University of Beirut,Lebanon

Keywords: TLR-5, flagellin, Anti-mTLR5-IgG, TLR-4, LPS-RS, cytokines.

Abstract: 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.

Cite this article as:

Mcheik Soha , Al-Akl S. Nayla and Abdelnoor M. Alexander *, The Effect of Denatured Flagellin on Toll-Like Receptor-5 (TLR-5) in Mice, Endocrine, Metabolic & Immune Disorders - Drug Targets 2018; 18 (4) . https://dx.doi.org/10.2174/1871530318666180327115448