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IL-1/TNF-? Inflammatory and Anti-Inflammatory Synchronization Affects Gingival Stem/Progenitor Cells' Regenerative Attributes.

ABSTRACT: Cytokines play major roles in tissue destruction/repair. The present study investigates proliferative and osteogenic differentiation potentials of gingival mesenchymal stem/progenitor cells (G-MSCs), influenced by IL-1/TNF-? inflammatory/anti-inflammatory conditions. Human G-MSCs were isolated, characterized, and cultured in basic medium (control group, M1), in basic medium with IL-1?, TNF-?, and IFN-? (inflammatory group, M2) and with IL-1ra/TNF-?i added to M2 (anti-inflammatory group, M3). MTT tests at days 1, 3, and 7 and CFU assay at day 12 were conducted. Osteogenic differentiation was analyzed by bone-specific transcription factors (RUNX2), alkaline phosphatase (ALP), type I collagen (Col-I), osteopontin (OPN), and osteonectin (ON) expression at days 1, 3, 7, and 14 and Alizarin red staining at day 14. At day 3, the control group showed the highest cell numbers. At day 7, cell numbers in inflammatory and anti-inflammatory group outnumbered the control group. At day 12, CFUs decreased in the inflammatory and anti-inflammatory groups, with altered cellular morphology. The anti-inflammatory group demonstrated elevated bone-specific transcription factors at 14 days. After 14 days of osteogenic induction, calcified nodules in the anti-inflammatory group were higher compared to control and inflammatory groups. For regeneration, initial inflammatory stimuli appear essential for G-MSCs' proliferation. With inflammatory persistence, this positive effect perishes and is followed by a short-term stimulatory one on osteogenesis. At this stage, selective anti-inflammatory intervention could boost G-MSCs' differentiation.

SUBMITTER: Zhang F

PROVIDER: S-EPMC5700502 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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IL-1/TNF-α Inflammatory and Anti-Inflammatory Synchronization Affects Gingival Stem/Progenitor Cells' Regenerative Attributes.

Zhang Fan F Si Misi M Wang Huiming H Mekhemar Mohamed K MK Dörfer Christof E CE Fawzy El-Sayed Karim M KM

Stem cells international 20171109

Cytokines play major roles in tissue destruction/repair. The present study investigates proliferative and osteogenic differentiation potentials of gingival mesenchymal stem/progenitor cells (G-MSCs), influenced by IL-1/TNF-α inflammatory/anti-inflammatory conditions. Human G-MSCs were isolated, characterized, and cultured in basic medium (control group, M1), in basic medium with IL-1β, TNF-α, and IFN-γ (inflammatory group, M2) and with IL-1ra/TNF-αi added to M2 ...[more]

PMID: 29250118

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Project description:ObjectiveAscorbic acid (AA) and controlled inflammatory stimuli are postulated to possess the ability to independently exert positive effects on a variety of proliferative, pluripotency, and differentiation attributes of gingival mesenchymal stem/progenitor cells (G-MSCs). The current study's objective was to explore and compare for the first time the impact of the major inflammatory cytokines (IL-1β/TNF-α/IFN-γ), AA, or their combination on multipotency/pluripotency, proliferative, and differentiation characteristics of G-MSCs.DesignHuman G-MSCs (n = 5) were isolated and cultured in basic medium (control group), in basic medium with major inflammatory cytokines; 1 ng/ml IL-1β, 10 ng/ml TNF-α, and 100 ng/ml IFN-γ (inflammatory group), in basic medium with 250 μmol/l AA (AA group) and in inflammatory medium supplemented by AA (inflammatory/AA group). All media were renewed three times per week. In stimulated G-MSCs intracellular β-catenin at 1 hour, pluripotency gene expression at 1, 3, and 5 days, as well as colony-forming units (CFUs) ability and cellular proliferation over 14 days were examined. Following a five-days stimulation in the designated groups, multilineage differentiation was assessed via qualitative and quantitative histochemistry as well as mRNA expression.Resultsβ-Catenin significantly decreased intracellularly in all experimental groups (p = 0.002, Friedman). AA group exhibited significantly higher cellular counts on days 3, 6, 7, and 13 (p < 0.05) and the highest CFUs at 14 days [median-CFUs (Q25/Q75); 40 (15/50), p = 0.043]. Significantly higher Nanog expression was noted in AA group [median gene-copies/PGK1 (Q25/Q75); 0.0006 (0.0002/0.0007), p < 0.01, Wilcoxon-signed-rank]. Significant multilineage differentiation abilities, especially into osteogenic and chondrogenic directions, were further evident in the AA group.ConclusionsAA stimulation enhances G-MSCs' stemness, proliferation, and differentiation properties, effects which are associated with a Wnt/β-catenin signaling pathway activation. Apart from initially boosting cellular metabolism as well as Sox2 and Oct4A pluripotency marker expression, inflammation appeared to attenuate these AA-induced positive effects. Current results reveal that for AA to exert its beneficial effects on G-MSCs' cellular attributes, it requires to act in an inflammation-free microenvironment.

Project description:Malaria, blood-borne filarial worms and intestinal parasites are all endemic in Gabon. This geographical co-distribution leads to polyparasitism and, consequently, the possibility of immune-mediated interactions among different parasite species. Intestinal protozoa and helminths could modulate antimalarial immunity, for example, thereby potentially increasing or reducing susceptibility to malaria. The aim of the study was to compare the cytokine levels and cytokine ratios according to parasitic profiles of the population to determine the potential role of co-endemic parasites in the malaria susceptibility of populations. Blood and stool samples were collected during cross-sectional surveys in five provinces of Gabon. Parasitological diagnosis was performed to detect plasmodial parasites, Loa loa, Mansonella perstans, intestinal helminths (STHs) and protozoan parasites. Nested PCR was used to detect submicroscopic plasmodial infection in individuals with negative blood smears. A cytometric bead array was used to quantify interleukin (IL)-6, IL-10 and tumour necrosis factor (TNF)-α in the plasma of subjects with different parasitological profiles. Median IL-6 and IL-10 levels and the median IL-10/TNF-α ratio were all significantly higher among individuals with Plasmodium (P.) falciparum infection than among other participants (p<0.0001). The median TNF-α level and IL-10/IL-6 ratio were higher in subjects with STHs (p = 0.09) and P. falciparum-intestinal protozoa co-infection (p = 0.04), respectively. IL-6 (r = -0.37; P<0.01) and IL-10 (r = -0.37; P<0.01) levels and the IL-10/TNF-α ratio (r = -0.36; P<0.01) correlated negatively with age. Among children under five years old, the IL-10/TNF-α and IL-10/IL-6 ratios were higher in those with intestinal protozoan infections than in uninfected children. The IL-10/TNF-α ratio was also higher in children aged 5-15 years and in adults harbouring blood-borne filariae than in their control counterparts, whereas the IL-10/IL-6 ratio was lower in those aged 5-15 years with filariae and intestinal parasites but higher in adults with intestinal parasitic infections. Asymptomatic malaria is associated with a strong polarization towards a regulatory immune response, presenting high circulating levels of IL-10. P. falciparum/intestinal protozoa co-infections were associated with an enhanced IL-10 response. Immunity against malaria could differ according to age and carriage of other parasites. Helminths and intestinal protozoa can play a role in the high susceptibility to malaria currently observed in some areas of Gabon, but further investigations are necessary.

Dataset Information

IL-1/TNF-? Inflammatory and Anti-Inflammatory Synchronization Affects Gingival Stem/Progenitor Cells' Regenerative Attributes.

Publications

IL-1/TNF-<i>α</i> Inflammatory and Anti-Inflammatory Synchronization Affects Gingival Stem/Progenitor Cells' Regenerative Attributes.

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