Whole‐Blood Cultures From Patients With Chronic Periodontitis Respond Differently to Porphyromonas gingivalis but not Escherichia coli Lipopolysaccharide

Abstract

Background: Porphyromonas gingivalis lipid A heterogeneity modulates cytokine expression in human cells. This study investigates the effects of two lipid A isoforms of P. gingivalis, lipopolysaccharide (LPS)1435/1449 and LPS1690, on the secretion of proinflammatory and regulatory cytokines in total blood cultures from patients with and without chronic periodontitis (CP).Methods: A cross‐sectional study was conducted in 38 systemically healthy individuals divided in two groups: 1) the CP group (n = 19), in which patients were diagnosed with CP; and 2) the no periodontitis (NP) group (n = 19), which included control patients without CP. Blood samples were collected from all patients, and whole‐blood cell cultures (WBCCs) were stimulated for 48 hours with P. gingivalis LPS1435/1449 and LPS1690 and Escherichia coli LPS. Unstimulated WBCCs served as negative controls. The secretion of interferon‐γ (IFN‐γ), interleukin‐10 (IL‐10), and transforming growth factor‐β (TGF‐β) was detected in WBCC supernatants by enzyme‐linked immunosorbent assays.Results: E. coli LPS significantly increased the expression of all cytokines in WBCCs from both the NP and CP groups when compared to non‐stimulated cells (control treatment). P. gingivalis LPS preparations increased IFN‐γ levels in the CP group but not in the NP group when compared with controls (P <0.05). P. gingivalis LPS preparations also increased IL‐10 and TGF‐β levels in both CP and NP groups, but P. gingivalis LPS1690 showed a three‐fold increase on IL‐10 production in the NP group (P <0.05) when compared to P. gingivalis LPS1435/144.Conclusions: These data demonstrate that WBCC cell populations obtained from healthy individuals and patients with CP may differ in the cytokine response to P. gingivalis but not E. coli LPS. This is consistent with the notion that CP alters the systemic WBCC response and that this can be detected by the different P. gingivalis LPS structures.

Application of the In Vitro HoxB8 Model System to Characterize the Contributions of Neutrophil–LPS Interaction to Periodontal Disease

“…Moreover, our observations support already-published results and further indicate that P. gingivalis manipulates intracellular signaling pathways in order to inhibit neutrophil survival, induce the secretion of pro-inflammatory cytokines and trigger oxidative burst, all of which promote periodontal disease progression. Taken together, this might contribute to the observed tissue damage in an in vivo mouse model of periodontitis as well as in periodontitis patients [ 24 , 25 ]. It is especially important as this periodontopathogen is an asaccharolytic organism that requires peptides and hemin for growth [ 26 ], which are products of the inflammatory breakdown of the host connective tissue [ 27 , 28 ].…”

La modulación de la expresión de IL-10 por el polimorfismo IL-10-592C/A (rs1800872) es independiente de la presencia y carga bacteriana de los periodontopatógenos clásicos

“…Desde la perspectiva de nuestro entendimiento actual de la patogénesis de la periodontitis parece razonable pensar que los periodontopatógenos del complejo rojo, clásicamente asociados a la ocurrencia, severidad y extensión de la periodontitis, estén directamente asociados con la producción de citoquinas proinflamatorias (consideradas clásicamente «destructivas») 9,10 , y no se asocien fuertemente a la expresión de una citoquina con un papel eminentemente supresor y «protector», como la IL-10. Sin embargo, como ya fue mencionado anteriormente, estudios previos han demostrado que los periodontopatógenos pueden inducir la sobreexpresión de IL-10, tanto in vivo como in vitro 11,12 . En este contexto, nuestros resultados sugieren que la regulación de los niveles de expresión de la IL-10 se encuentra fuertemente influenciada por el perfil genético del hospedero, y que los estímulos microbiológi-cos, así como los mecanismos de regulación compensatorios del hospedero, solo desempeñarían un rol secundario 19 .…”

“…De modo interesante, a pesar de la demostrada asociación entre las baterías periodontopatógenas putativas con la severidad, extensión y respuesta al tratamiento de la periodontitis crónica, también ha sido demostrado que la infección bacteriana por periodontopatógenos no solo estimula la expresión de citoquinas proinflamatorias, sino que ejerce un efecto estimulante en la expresión de mediadores antiinflamatorios (como IL-10) 11,12 . A pesar de lo anterior, hasta el momento ningún estudio ha investigado específicamente el rol de la infección por periodontopatógenos en la regulación de los niveles de expresión de IL-10 en la presencia o ausencia de variaciones genéticas polimórficas en IL-10-592C/A.…”

Lipoteichoic Acid (LTA) and Lipopolysaccharides (LPS) from Periodontal Pathogenic Bacteria Facilitate Oncogenic Herpesvirus Infection within Primary Oral Cells

“…Interestingly, one recent study demonstrates that P. gingivalis LPS and Escherichia coli LPS differently regulate cytokine production in human gingival fibroblasts [64]. Another recent study indicates that whole blood cell cultures (WBCC) populations obtained from healthy and chronic periodontitis patients may differ in the cytokine response to P. gingivalis LPS but not E. coli LPS [65]. In fact, P. gingivalis- derived LPS exhibits unique features compared with the LPS of other species, including differences in the structure of the O-antigen, as well as in the acylation patterns and receptor-activating capacities of the lipid A component [66]–[68].…”