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1. Xanthan gum protects temporomandibular chondrocytes from IL‑1β through Pin1/NF‑κB signaling pathway.

Author

Yuan F, Xie JL, Liu KY, Shan JL, Sun YG, and Ying WG

Subjects
Animals, Cell Survival drug effects, Cells, Cultured, Chemokine CCL2 metabolism, Interleukin-1beta pharmacology, Male, Matrix Metalloproteinases metabolism, Nitric Oxide Synthase Type II metabolism, Protective Agents pharmacology, Rats, Rats, Sprague-Dawley, Signal Transduction, Temporomandibular Joint Disorders chemically induced, Temporomandibular Joint Disorders drug therapy, Adaptor Proteins, Signal Transducing metabolism, Chondrocytes drug effects, Cytokines metabolism, Polysaccharides, Bacterial pharmacology, Transcription Factor RelA metabolism
Abstract

Temporomandibular disorder (TMD) is a complicated and multi‑factorial disease related to inflammation and cartilage destruction. Intra‑articular injection of xanthan gum (XG) has been demonstrated to protect the joint cartilage and reduce osteoarthritis progression. However, the role and mechanism of XG in TMD is still unclear. In the present study, chondrocytes were isolated from rats and identified by immunofluorescence. Cells were stimulated by XG or interleukin (IL)‑1β. Cell viability was analyzed by MTT assay. Tumor necrosis factor α (TNF‑α) and IL‑6 levels were determined by ELISA. The expression of monocyte chemoattractive protein‑1 (MCP‑1), inducible nitric oxide synthase (iNOS), collagens, matrix metalloproteinases (MMPs), peptidyl‑prolyl isomerase 1 (Pin1) and phosphorylated nuclear factor κB (NF‑κB) p65 (p‑p65) was analyzed by quantitative PCR or western blotting. MMP activity was assessed by gelatin zymography. Compared with the control, XG treatment partially reversed the IL‑1β‑reduced cell viability. In addition, IL‑1β stimulation increased inflammatory cytokine expression, including TNF‑α, IL‑6 secretion, MCP‑1 and iNOS expression, whereas XG treatment reduced the expression of these inflammatory cytokines compared with that of the IL‑1β‑stimulated cells. Additionally, XG increased the expression of collagen, but reduced MMP expression and activity as compared with that in the IL‑1β group. In addition, XG treatment prevented the IL‑1β‑increased Pin1 and p‑p65 expression. These data suggested that XG reduced the expression of inflammatory cytokines and may maintain the balance between collagens and MMPs partially through the Pin1/NF‑κB signaling pathway in IL‑1β‑stimulated temporomandibular chondrocytes. Therefore, XG may be useful in the treatment of TMD.

Published
2020
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2. Clinical development of a VAR2CSA-based placental malaria vaccine PAMVAC : quantifying vaccine antigen-specific memory B & T cell activity in Beninese primigravidae

Author

Gbedande, K., Fievet, Nadine, Viwami, F., Ezinmegnon, S., Issifou, S., Chippaux, Jean-Philippe, Dossou, Y., Moutairou, K., Massougbodji, A., Ndam, N., de Jongh, W. A., Sogaard, T. M. M., Salanti, A., Nielsen, M. A., Esen, M., Mordmuller, B., Deloron, Philippe, Luty, Adrian, and Multi-Centre Research Paper

Subjects
T & B cells, Pregnancy, parasitic diseases, Cytokines, VAR2CSA, Vaccine, Malaria
Abstract

Background: The antigen VAR2CSA plays a pivotal role in the pathophysiology of pregnancy-associated malaria (PAM) caused by Plasmodium falciparum. A VAR2CSA-based vaccine candidate, PAMVAC, is under development by an EU-funded multi-country consortium (PlacMalVac project). As part of PAMVACs clinical development, we quantified naturally acquired vaccine antigen-specific memory B and T cell responses in Beninese primigravidae recruited at the beginning of pregnancy and followed up to delivery and beyond. Methods: Clinical and parasitological histories were compiled from monthly clinic visits. On 4 occasions (first and fifth month of pregnancy, delivery, 6 months post-delivery) peripheral blood mononuclear cells were isolated for in vitro assays. PAMVAC-specific memory B cells as well as those specific for a PAM unrelated P. falciparum antigen (PfEMP1-CIDR1a) and for tetanus toxoid were quantified by ELISpot. Memory T cell responses were assessed by quantifying cytokines (IL-5, IL-6, IL-10, IL-13, IFN-gamma, TNF-alpha) in supernatants of cells stimulated in vitro either with PAMVAC, or mitogen (PHA). Results: Both tetanus toxoid- and PAMVAC-specific memory B cell frequencies increased to reach peak levels in the 5th month and at delivery, respectively and persisted post-delivery. The frequency of CIDR1a-specific memory B cells was stable during pregnancy, but declined post-delivery. The cumulated prevalence of infection with P. falciparum during pregnancy was 61% by microscopy. In women with a history of such infections, a significantly higher frequency of PAMVAC-specific memory B cells was observed at delivery. PAMVAC-specific pro-inflammatory (IFN-gamma, TNF) responses tended to be higher at delivery in those with a history of infection. Mitogen-induced IL-5/IL-13 responses were significantly enhanced in the same women. Conclusions: PAMVAC-specific memory B cells are induced during first pregnancies and are maintained post-delivery. Women with a T helper cell profile biased towards production of Th2-type cytokines have a greater risk of infection with P. falciparum.

Published
2017