Polyamines suppress Toll-like receptor 4 signaling in neutrophil-like cells

Autor: Kai-Fan Chen, 陳凱芳
Rok vydání: 2013
Druh dokumentu: 學位論文 ; thesis
Popis: 101
Neutrophils are the first immune cells to arrive at sites of infection. Bacterial products induce the release of proinflammatory cytokines in neutrophils. Lipopolysaccharide (LPS) is the principal outer membrane component of Gram-negative bacteria that activates Toll-like receptor 4 (TLR4) signaling pathway. TLR4 is one of the most important regulators of neutrophil activation. Polyamines play an important role in many biological functions, including cell cycle, proliferation and immunomodulation. Polyamines specifically suppress the synthesis of proinflammatory cytokines. However, how it regulates the immune responses is still unclear. Therefore, we examined whether polyamines regulated TLR4 signaling to inhibit proinflammatory cytokines. In this study, we found that polyamines inhibited TLR4 protein and mRNA expression. Moreover, polyamines repressed IL-1b expression in neutrophil-like cells to response LPS. In addition, a NF-kB inhibitor BAY-11-7082 and an AP-1 inhibitor curcumin suppressed TLR4 expression in neutrophil-like cells. We further found polyamines inhibited NF-kB and AP-1 expression in neutrophil-like cells. These results demonstrated that polyamines could inhibit TLR4 signaling through repressing proinflammatory transcription factors NF-kB and AP-1 expression in neutrophil-like cells.
Databáze: Networked Digital Library of Theses & Dissertations