Hypoxia enhances the effect of lipopolysaccharide-stimulated IL-1β expression in human periodontal ligament cells

Abstract

Oral infection is inflammatory disease caused by bacteria. A major component of gram negative bacteria membrane associated with inflammation is lipopolysaccharide (LPS). Currently, evidence presenting the combined effect of LPS and hypoxia to inflammatory response in human periodontal ligament cells (HPDLs) was yet lacking. Here, we studied whether the influence of oxygen on LPS-stimulated inflammatory cytokines in HPDLs. HPDLs were stimulated with LPS in normoxia and hypoxia for 24 h. The mRNA and protein expression of inflammatory cytokines were examined by polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The intracellular mechanisms of these effects were investigated by chemical inhibitors and small interfering RNA (siRNA). The results showed that LPS-stimulated IL-1β, IL-6, IL-8 in HPDLs in both hypoxia and normoxia. Hypoxia condition enhanced the effect of LPS-stimulated cytokines expression. Apigenin, the hypoxia-inducible factors (HIF)-1α inhibitor, totally prevented LPS-stimulated IL-1β expression in both normoxia and hypoxia. Similar to knockout HIF-1α gene expression by siRNA did \not prevent LPS-stimulated IL-1β expression. These data concluded that hypoxia increased virulence of LPS-stimulated IL-1β production in HPDLs.

Porphyromonas gingivalis lipopolysaccharide regulates ephrin/Eph signalling in human periodontal ligament fibroblasts

“…However, these data are not comparable to the LPS dose used in in‐vitro studies as the LPS contained in the serum is pretty low and that measured in gingival crevicular fluid is presented with the activity of the endotoxin. Thus, we referred to the corresponding in‐vitro research and chose the most commonly used quantities of P. gingivalis LPS for our experiment planning.…”

“…To test the dose‐dependent effects, the PDLFs were cultured in the presence of P. gingivalis LPS at concentrations of 0.001, 0.01, 0.1, 1 and 10 μg/mL for 24 hours. The concentrations of P. gingivalis LPS (0.001‐10 μg/mL) we selected, which could be refined to different experiment protocols, are based on previous research regarding the in‐vitro PDLF cultures . To investigate the time‐dependent effects, P. gingivalis LPS of the optimal concentration (0.1 μg/mL) was used to stimulate the PDLFs for different experimental periods (6, 12, 24 and 48 hours).…”

Serum Inflammatory Factor Profiles in the Pathogenesis of High-Altitude Polycythemia and Mechanisms of Acclimation to High Altitudes

“…IL-1 beta is produced by activated macrophage and stimulates the maturation and proliferation of B cells and the release of more inflammatory mediators, which results in inflammation and tissue damage [ 25 ]. Also, high-altitude and hypoxia conditions could enhance IL-1 beta secretion [ 22 , 25 , 26 ]. IL-2, which is known as a T cell survival factor, plays a key role in immunity.…”

Role of the Hypoxia-Inducible Factor in Periodontal Inflammation

“…Recent studies reported that a hypoxic environment may upregulate proinlammatory cytokines and MMPs' expression from host cells during periodontal disease [34]. The idea was that hypoxia further encourages lipopolysaccharide (LPS)-induced TNF-α, interleukin-1β, and interleukin 6 (IL-6) expressions via LPS toll-like receptor (TLR) interaction that, in turn, activates the nuclear factor kappa B (NF-κB) pathway in human PDL cells upon exposure to the aforementioned Gram-negative bacterial surface component [35][36][37].…”