Elastin-Derived Peptides Induce Inflammatory Responses through the Activation of NF-κB in Human Ligamentum Flavum Cells

Abstract

The formation of fibrotic tissue in the ligamentum flavum (LF) is usually preceded by breakdown of elastic fibers. Elastin-derived peptides (EDPs) from breakdown of elastic fibers display a wide range of biological activities in a variety of cells, but there is minimal information regarding the involvement in the processes of LF hypertrophy. The aim of this study is to elucidate the effects of EDPs on cultured human LF cells and to investigate their molecular and biochemical mechanisms. Human LF cells were obtained from 18 patients who underwent lumbar spine surgery. After treatment with different concentrations of EDPs with or without specific inhibitors in culture medium, the viability and proliferation of LF cells, genes expression, and the signaling pathways were evaluated and analyzed. It was found that 50 μg/ml EDPs significantly increased cell proliferation and synthesis of prostaglandin E(2). The gene expression and protein production of proinflammatory cytokines, including interleukin-1α (IL-1α), IL-1β, and IL-6, were also upregulated. The levels of p-ERK (extracellular signal-regulated kinase) and NF-κB increased immediately following EDP treatment and sustained up to 90 min. It was also found that NF-κB inhibitor, but not ERK1/2 inhibitor, attenuated EDP-dependent induction of IL-1α, IL-1β, and IL-6 expression, indicating that NF-κB pathways are required for EDP-induced IL-1α, IL-1β, and IL-6 gene expression in human LF cells. The results of this in vitro experiment suggest that EDPs do induce inflammatory responses in human LF cells and plays the key role in the development of LF hypertrophy.

Stromal Androgen Receptor in Prostate Cancer Development and Progression

“…The ECM can also drive cancer cell gene expression, signal transduction, cell morphology, cell survival, and motility [ 124 ]. Changes in ECM can also cause CAFs to secret pro-inflammatory markers, thereby enhancing cancer progression [ 125 , 126 ]. In physical terms, it appears that the ECM can regulate cancer cell invasion via multiple parameters, including density, orientation, stiffness, and organisation of the matrix fibres.…”

Tissue transglutaminase is involved in mechanical load–induced osteogenic differentiation of human ligamentum flavum cells

“…TGM2 also can be induced directly by NF-κB activation to modulate inflammatory response (12). Furthermore, elastin-derived peptides from breakdown of elastic fibers could also induce inflammatory responses through the activation of NF-κB cascades (43). This study further demonstrates that centrifugal force induces TGM2 gene expression and enzyme activity in human ligamentum flavum cells.…”

Leptin-induced inflammation by activating IL-6 expression contributes to the fibrosis and hypertrophy of ligamentum flavum in lumbar spinal canal stenosis

“…NF-κB is highly activated at sites of inflammation in diverse diseases and can induce transcription of proinflammatory cytokines, chemokines, adhesion molecules, and inducible enzymes, mainly mediating cellular responses to damage, stress, and inflammation [ 29 ]. It has been reported that NF-κB plays a crucial role in the production of inflammatory mediators in LF tissues induced by many cytokines or proteins [ 17 , 30 ]. Here, we also found that the NF-κB pathway was essential for leptin-induced IL-6 expression in LF cells.…”