Biomedical subjects

Sylvie Fournel

Publications and source records attributed to Sylvie Fournel.

9 recordsLinked to original sources

PubMed2026

Complementary activity of an ancient combination of natural ingredients on the dysbiosis symptoms linked to acne.

ETHNOPHARMACOLOGICAL RELEVANCE: Acne is one of the most common dermatologic diseases in the world. It is due to the secretion of a high level of sebum that causes follicular hyperkeratinisation, alterations of the cutaneous microbiota, and inflammatory processes. One of the first-line treatments is still an antibiotic prescription, that inhibits bacterial growth and, as a consequence, lowers some of the other symptoms. Nevertheless, this high level of antibiotic prescription contributes to the increase of antibiotic resistance. Alternatives to antibiotics are thus highly required, as acne does not represent per se an infection. AIM OF THE STUDY: In the frame of the IRGAP (Interdisciplinary Research Group on Ancient Pharmacopeias) consortium, different preparations dedicated to cutaneous ailments have been identified based on ancient traditional uses, dating back to Antiquity or Middle Ages. Among them, the combination of Aloe vera and Myrrh was widely conserved over centuries. Even though this combination is no longer in use, we wondered why this combination was so widely conserved. We considered the use of this combination of ingredients to treat acne, a case study for which both plants are still used, but separately. MATERIALS AND METHODS: The effects of both plant extracts were analyzed on the growth of different bacteria from the skin microbiota, cultivated alone or in co-culture conditions. As the skin is a rather heterologous environment, we further tested the robustness of our study by varying the experimental conditions. We further analyzed any complementary effects of these extracts on the inflammation process linked to acne. RESULTS: We showed that both plant extracts have complementary effects on micro-organisms and on macrophages. Indeed, while Myrrh extracts inhibited the growth of specific skin microbiota bacteria, Aloe vera gel extracts on the opposite, favored the growth of others: the two plants could act in a complementary way to restore a healthy microbiota. Another complementarity was also observed on macrophages: while Myrrh extracts showed an anti-inflammatory effect, Aloe vera gel extracts showed an antioxidant effect. CONCLUSION: Our results highlight the potential of the combination of Myrrh and Aloe vera to address both the dysbiosis of the skin microbiota and the inflammation associated with acne. Thus, this exploration of forgotten combinations from historical pharmacopoeias underscores the importance of revisiting past traditional knowledge as a source of innovation.

Aloe vera↗

PubMed2006

Soluble HLA-G1 inhibits angiogenesis through an apoptotic pathway and by direct binding to CD160 receptor expressed by endothelial cells.

HLA-G is a major histocompatibility complex class Ib molecule whose constitutive tissue distribution is restricted mainly to trophoblast cells at the maternal-fetal interface during pregnancy. In this study, we demonstrated the ability of the soluble HLA-G1 (sHLA-G1) isoform to inhibit fibroblast growth factor-2 (FGF2)-induced capillary-like tubule formation. Using a rabbit corneal neovascularization model, we further showed that sHLA-G1 inhibits FGF2-induced angiogenesis in vivo. We also demonstrated that sHLA-G1 induces endothelial cell apoptosis through binding to BY55/CD160, a glycosylphosphatidylinositolanchored receptor expressed by endothelial cells. Furthermore, we showed that the specific CL1-R2 anti-CD160 monoclonal antibody mimics sHLA-G1-mediated inhibition of endothelial cell tube formation and induction of apoptosis. Thus, the engagement of CD160 in endothelial cells may be essential for the inhibition of angiogenesis. sHLA-G1/CD160-mediated antiangiogenic property may participate in the vascular remodeling of maternal spiral arteries during pregnancy, and, given that we found that CD160 is strongly expressed in the vasculature of a murine tumor, it offers an attractive therapeutic target for preventing pathologic neovascularization.

Amino Acid Sequence↗

PubMed2006

Solid-phase synthesis of CD40L mimetics.

The C3-symmetric molecule has been previously shown to mimic CD40 ligand (CD40L) homotrimers and to display effector functions. This molecule consists of a cyclic hexapeptide core containing the repetition of the D-Ala-L-Lys motif. The side chains of the lysine residues have been modified by appending the CD40L-derived sequence 143Lys-Gly-Tyr-Tyr146 via a 6-aminohexanoic acid residue as a spacer. The present report describes a general solid-phase synthesis approach to and related trimeric architectures. In addition, their CD40 binding properties as well as their effector functions have been evaluated.

Apoptosis↗

PubMed2006

Mimicking helical antibacterial peptides with nonpeptidic folding oligomers.

Unnatural oligomeric scaffolds designed to adopt defined secondary structures (e.g., helices), while retaining the chemical diversity of amino acid side chains, are of practical value to elaborate functional mimetics of bioactive alpha-polypeptides. Enantiopure N,N'-linked oligoureas as short as seven residues long have been previously shown to fold into a stable helical structure, stabilized by 12- and 14-membered H-bonded rings. We now report that eight-residue oligoureas designed to mimic globally amphiphilic alpha-helical host-defense peptides are effective against both gram-negative and gram-positive bacteria (including methicillin-resistant Staphylococcus aureus [MRSA]) and exhibit selectivity for bacterial versus mammalian cells. Circular dichroism (CD) spectroscopy studies suggest enhanced helical propensity of oligoureas in the presence of phospholipid vesicles. The utility of this new class of nonpeptidic foldamers for biological applications is highlighted by high resistance to proteolytic degradation.

Amino Acid Sequence↗

PubMed2005

C3-symmetric peptide scaffolds are functional mimetics of trimeric CD40L.

Interaction between CD40, a member of the tumor necrosis factor receptor (TNFR) superfamily, and its ligand CD40L, a 39-kDa glycoprotein, is essential for the development of humoral and cellular immune responses. Selective blockade or activation of this pathway provides the ground for the development of new treatments against immunologically based diseases and malignancies. Like other members of the TNF superfamily, CD40L monomers self-assemble around a threefold symmetry axis to form noncovalent homotrimers that can each bind three receptor molecules. Here, we report on the structure-based design of small synthetic molecules with C3 symmetry that can mimic CD40L homotrimers. These molecules interact with CD40, compete with the binding of CD40L to CD40, and reproduce, to a certain extent, the functional properties of the much larger homotrimeric soluble CD40L. Architectures based on rigid C3-symmetric cores may thus represent a general approach to mimicking homotrimers of the TNF superfamily.

Animals↗

PubMed2003

CD4+ T cells from (New Zealand Black x New Zealand White)F1 lupus mice and normal mice immunized against apoptotic nucleosomes recognize similar Th cell epitopes in the C terminus of histone H3.

We have previously reported that peptide 88-99 of histone H4 represents a minimal T cell epitope recognized by Th cells from nonautoimmune BALB/c (H-2(d/d)) mice immunized with nucleosomes. In this study, we tested a panel of overlapping peptides spanning the whole sequences of H4 and H3 for recognition by CD4(+) T cells from unprimed (New Zealand Black (NZB) x New Zealand White (NZW))F(1) lupus mice (H-2(d/z)). None of the 11 H4 peptides was recognized by CD4(+) T cells from (NZB x NZW)F(1) mice. In contrast, these cells proliferated and secreted IL-2, IL-10, and IFN-gamma upon ex vivo stimulation with H3 peptides representing sequences 53-70, 64-78, and 68-85. Peptides 56-73 and 61-78 induced the production of IFN-gamma and IL-10, respectively, without detectable proliferation, suggesting that they may act as partial agonist of the TCR. Th cells from unprimed BALB/c mice and other lupus-prone mice such as SNF(1) (H-2(d/q)) and MRL/lpr (H-2(k/k)) mice did not recognize any peptides present within the H3 region 53-85. We further demonstrated that immunization of normal BALB/c mice with syngeneic liver nucleosomes and spleen apoptotic cells, but not with nonapoptotic syngeneic cells, induced Th cell responses against several peptides of the H3 region 53-85. Moreover, we found that this conserved region of H3, which is accessible at the surface of nucleosomes, is targeted by Abs from (NZB x NZW)F(1) mice and lupus patients, and contains motifs recognized by several distinct HLA-DR molecules. It might thus be important in the self-tolerance breakdown in lupus.

Amino Acid Sequence↗

PubMed2003

Functional antibodies to leukocyte adhesion molecules in antithymocyte globulins.

BACKGROUND: Polyclonal antithymocyte globulins (ATG) induce T-cell depletion and functional impairment of nondeleted lymphocytes. Interference of ATG with the main leukocyte surface molecules involved in cellular adhesion and leukocyte-endothelium interaction was investigated in the present study. METHODS: In three rabbit ATG, the authors measured antibodies to integrins, beta2-integrin ligands, and chemokine receptors by flow cytometry; chemotactic responses; and down-modulation of cell surface expression on lymphocytes, monocytes, and neutrophils. RESULTS: Antibodies to CD11a/CD18 (leukocyte function-associated antigen-1 [LFA-1]) present in ATG induced a dose-dependent down-modulation of cell surface expression of this beta2 integrin on lymphocytes, monocytes, and neutrophils. In contrast, anti-LFA-1 monoclonal antibodies did not induce LFA-1 modulation unless cross-linked by a second antibody. ATG also contained functional antibodies to the beta1 integrin CD49d/CD29 (VLA-4), the alpha4beta7 integrin, CD50, CD54, and CD102 but not to CD62L. ATG were shown to bind to CXCR4 and CCR7 on lymphocytes, CXCR4, and CCR5 on monocytes; to down-modulate cell surface expression of CCR7; and to decrease monocyte chemotactic response to CCL5 (RANTES) and lymphocyte chemotactic response to CCL19 (MIP-3beta). CONCLUSION: These results show that ATG may interfere with leukocyte responses to chemotactic signals but mostly inhibit the expression of integrins required for firm cellular adhesion. The latter property of inhibition is not shared by monoclonal antibodies, and it may contribute to decreasing graft cellular infiltration during acute rejection and possibly after postischemic reperfusion.

Animals↗

PubMed2002

Autoantigen microarrays for multiplex characterization of autoantibody responses.

We constructed miniaturized autoantigen arrays to perform large-scale multiplex characterization of autoantibody responses directed against structurally diverse autoantigens, using submicroliter quantities of clinical samples. Autoantigen microarrays were produced by attaching hundreds of proteins, peptides and other biomolecules to the surface of derivatized glass slides using a robotic arrayer. Arrays were incubated with patient serum, and spectrally resolvable fluorescent labels were used to detect autoantibody binding to specific autoantigens on the array. We describe and characterize arrays containing the major autoantigens in eight distinct human autoimmune diseases, including systemic lupus erythematosus and rheumatoid arthritis. This represents the first report of application of such technology to multiple human disease sera, and will enable validated detection of antibodies recognizing autoantigens including proteins, peptides, enzyme complexes, ribonucleoprotein complexes, DNA and post-translationally modified antigens. Autoantigen microarrays represent a powerful tool to study the specificity and pathogenesis of autoantibody responses, and to identify and define relevant autoantigens in human autoimmune diseases.

Animals↗

PubMed2002

Anti-nucleosome antibodies and T-cell response in systemic lupus erythematosus.

Evidence accumulated in recent years suggests that nucleosomes play a pivotal role in the induction phase and pathogenesis of systemic lupus erythematosus (SLE). Apoptotic cells are an important source of nucleosomes and apoptosis defects have been described in patients with SLE as well as in lupus mice. Moreover, it has been demonstrated that the intravenous injection of apoptotic cells in normal mice generated the production of anti-nuclear antibodies and led to the development of symptoms associated with lupus disease. In this review, we briefly summarize these results and describe recent findings on the characterization of histone T-cell epitopes recognized by CD4(+) cells from different strains of lupus mice. We have tested a panel of overlapping peptides spanning the whole sequences of H4 and H3 histones for recognition by CD4(+) T cells from unprimed (NZBxNZW) F1 and MRL/lpr lupus mice. We have also immunized naïve BALB/c mice with nucleosomes or syngeneic apoptotic and non-apoptotic spleen cells, and tested the activation of Th cells reacting ex vivo with H4 and H3 peptides. Our results suggest that nucleosomes and apoptotic cells may effectively act as initiator of autoreactive Th cell development in lupus mice. In the BW lupus model, the region 53-85 of H3, which also contains B-cell epitopes recognized by antibodies from (NZBxNZW) F1 mice and lupus patients, might be important.

Animals↗