William Rostène

French National Centre for Scientific Research, Lutetia Parisorum, Île-de-France, France

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Publications (291)1008.22 Total impact

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    ABSTRACT: Ocular surface diseases are among the most frequent ocular pathologies, with prevalence ranging from 20% of the general population. In addition, ocular pain following corneal injury is frequently observed in clinic. The aim of the study was to characterize the peripheral and central neuroinflammatory process in the trigeminal pathways in response to cornea alteration induced by chronic topical instillations of 0.2% benzalkonium chloride (BAC) in male C57BL/6 J mice. In vitro BAC induced neurotoxicity and increases neuronal (FOS, ATF3) and pro-inflammatory (IL-6) markers in primary mouse trigeminal ganglion culture. BAC-treated mice exhibited 7 days after the treatment reduced aqueous tear production and increased inflammatory cell infiltration in the cornea. Hypertonic saline-evoked eye wipe behavior was enhanced in BAC-treated animals that exhibited increased FOS, ATF3 and Iba1 immunoreactivity in the trigeminal ganglion. Ocular inflammation is associated with a significant increase in IL-6 and TNF-α mRNA expression in the trigeminal ganglion. We reported a strong increase in FOS and Iba1 positive cells in particular in the sensory trigeminal complex at the ipsilateral interpolaris/caudalis (Vi/Vc) transition and Vc/upper cervical cord (Vc/C1) regions. In addition, activated microglial cells were tightly wrapped around activated FOS neurons in both regions and phosphorylated p38 mitogen-activated protein kinase was markedly enhanced specifically in microglial cells during ocular inflammation. Similar data were obtained in the facial motor nucleus. These neuroanatomical data correlated with the increase in mRNA expression of pro-inflammatory (TNF-α, IL-6, CCL2) and neuronal (FOS and ATF3) markers. Interestingly, the suppression of corneal inflammation 10 days following the end of BAC treatment resulted in a marked attenuation of peripheral and central changes observed in pathological conditions.
    No preview · Article · Dec 2015 · Neurobiology of Disease
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    ABSTRACT: Introduction: Glaucoma is a sight-threatening retinal neuropathy associated with elevated intraocular pressure (IOP) due to degeneration and fibrosis of the trabecular meshwork (TM). Glaucoma medications aim to reduce IOP without targeting the specific TM pathology, Bone-marrow mesenchymal stem cells (MSCs) are used today in various clinical studies. Here, we investigated the potential of MSCs therapy in an glaucoma-like ocular hypertension (OHT) model and decipher in vitro the effects of MSCs on primary human trabecular meshwork cells. Methods: Ocular hypertension model was performed by cauterization of 3 episcleral veins (EVC) of Long-Evans male rat eyes. MSCs were isolated from rat bone marrow, amplified in vitro and tagged with quantum dot nanocrystals. Animals were distributed as 1) MSCs group receiving 5.10(5)cells/6μl Minimum Essential Medium and 2) MEM group receiving 6μl MEM (n = 10 each). Injections were performed into the anterior chamber of 20 days-hypertensive eyes and IOP was monitored twice a week for 4 weeks. At the end of experiment, cell distribution in the anterior segment was examined in confocal microscopy on flat mounted corneas. Moreover, we tested in vitro effects of MSCs conditioned medium (MSC-CM) on primary human trabecular meshwork cells (hTM cells) using Akt activation, myosin phosphorylation and TGF-β2-dependent profibrotic phenotype in hTM cells. Results: We demonstrated a rapid and long-lasting in vivo effect of MSCs transplantation that significantly reduced IOP in hypertensive eyes induced by EVC. MSCs were located to the ciliary processes and the TM. Enumeration of RGCs on whole flat-mounted retina highlighted a protective effect of MSCs on RGCs death. In vitro, MSC-CM promotes: (i) hTM cells survival by activating the antiapoptotic pathway, Akt, (ii) hTM cells relaxation as analyzed by the decrease in myosin phosphorylation and (iii) inhibition of TGF-β2-dependent profibrotic phenotype acquisition in hTM cells. Conclusions: MSCs injection in the ocular anterior chamber in a rat model of OHT provides neuroprotective effect in the glaucoma pathophysiology via TM protection. These results demonstrate that MSCs constitute promising tool for treating ocular hypertension and retinal cell degeneration.
    Full-text · Article · Sep 2015 · Stem Cell Research & Therapy
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    ABSTRACT: Tissue clearing and subsequent imaging of intact transparent tissues have provided an innovative way to analyze anatomical pathways in the nervous system. In this study, we combined a recent 3-dimensional imaging of solvent cleared organ (3DISCO) procedure, light-sheet microscopy, fluorescent retrograde tracer, and Imaris software to 3D map corneal sensory neurons within a whole adult mouse trigeminal ganglion (TG). We first established the optimized steps to easily and rapidly clear a fixed TG. We found that the 3DISCO procedure gave excellent results and took less than 3 hours to clear the TG. In a second set of experiments, a retrograde tracer (cholera toxin B Alexa 594-conjugated) was applied to de-epithelialized cornea to retrograde-labeled corneal sensory neurons. Two days later, TGs were cleared by the 3DISCO method and serial imaging was performed using light-sheet ultramicroscopic technology. High-resolution images of labeled neurons can be easily and rapidly obtained from a 3D reconstructed whole mouse TG. We then provided a 3D reconstruction of corneal afferent neurons and analyzed their precise localization in the TG. Thus, we showed that neurons supplying corneal sensory innervation exhibit a highly specific limited dorsomedial localization within the TG. We report that our combined method offers the possibility to perform manual (on 20 μm sections) and automated (on 3D reconstructed trigeminal ganglion) counting of labeled cells in a cleared mouse TG. To conclude, we illustrate that the combination of the 3DISCO clearing method with light-sheet microscopy, retrograde tracer, and automatic counting represents a rapid and reliable method to analyze a subpopulation of neurons within the peripheral and central nervous system. Copyright © 2015. Published by Elsevier Ltd.
    Full-text · Article · Jun 2015 · Experimental Eye Research
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    ABSTRACT: Chemokines and opioids are important regulators of immune, inflammatory and neuronal responses in peripheral and central pain pathways. Recent studies have provided insights into the functional interactions between chemokine receptors and opioid receptors, and their role in pain modulation. In this Progress article, we discuss how crosstalk between these two systems might provide a molecular and cellular framework for the development of novel analgesic therapies for the management of acute and/or chronic pain.
    No preview · Article · Feb 2015 · Nature reviews Neuroscience
  • William Rostene · Thierry Rayer

    No preview · Article · Jan 2015 · Biologie Aujourd'hui
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    ABSTRACT: Chronic neuropathic pain has become a real social issue, due to the difficulty of its treatment and by the major impairment to quality of life that it causes in every day behavior. Understanding neurobiological basis and pathophysiological causes of diverse painful syndromes constantly evolves and reports the complexity of its mechanisms. Unfortunately this complexity makes it difficult to discover effective treatments against chronic pain syndromes, in particular as regards peripheral neuropathic pains. Recent studies reveal that, during chronic peripheral neuropathy, inflammatory mediators (in particular chemokines), besides their implications in the modulation of nociceptive messages and central neuroinflammatory mechanisms, play a critical role in the orchestration of the immune response induced by a peripheral nerve lesion. In this review, after a brief introduction about chemokines and their role in neuromodulation of the nociceptive message, we will attempt to define their functions and implications in the immune response associated to peripheral neuropathies. Thus, perfectly understanding the molecular and cellular communications between the nervous system and the immune system will be useful for the future development of novel and innovative therapeutic strategies against these highly disabling pathologies.
    No preview · Article · Jun 2014 · Biologie Aujourd'hui
  • Christophe Baudouin · Alexandre Denoyer · William Rostène
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    ABSTRACT: Second leading cause of blindness worldwide, glaucoma is an optic neuropathy related mainly but not exclusively to an increase of intraocular pressure. Angle closure glaucoma is related to a blockade of aqueous humor to the trabecular meshwork, whereas open-angle glaucoma is a degeneration of the trabecular meshwork, the filter that allows aqueous outflow from the eye. Many improvements have been made in terms of diagnosis, follow-up and treatments, although the treatment of glaucoma is restricted to control intraocular pressure, in order to prevent optic nerve degeneration or to stop the progression of the disease toward blindness. The first line therapy is based on topical medications that are administered for the whole life span. Although globally efficient, these treatments, and most likely the preservative included in the excipient to prevent bottle contamination, induce side effects in the long-term that may impair the quality of life, patient compliance or directly induce ocular surface changes like inflammatory cytokine release, or tear film destruction, with further dry eye disease and chronic inflammation. A large body of evidence has been accumulated, showing that benzalkonium chloride, the preservative mainly used, is toxic over the long run and plays a role in such ocular surface impairment. Therefore efforts have been made in the last decade to eliminate or replace this compound, providing safer therapies to the patients. Furthermore, the identification of chemokines as playing a role in the trabecular degeneration has open new directions for treating glaucoma. The blockade of one receptor of CXCL12 has been experimentally shown not only to decrease intraocular pressure but also to prevent trabecular cell degeneration. This is an innovative concept that could allow development of new treatments, more specifically targeting the disease at its onset, rather than attempting to reduce its progression in its later stages.
    No preview · Article · Oct 2013 · Biologie Aujourd'hui
  • William Rostene · Alexandre Denoyer · Christophe Baudouin
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    ABSTRACT: The celebrations of the 200th anniversary of Claude Bernard's birth (1813) give us the opportunity to recall all the pioneer work carried out by the great physiologist, which still remains relevant in both scientific and medical fields. The description that tissues are "floating in a liquid milieu" bringing survival molecules and allowing homeostasis, is particularly illustrated in the physiopathology of glaucoma. Second leading cause of blindness worldwide, glaucoma is an optic neuropathy mainly related to an increase of intraocular pressure. Degeneration of the trabecular meshwork, the filter that allows aqueous humor outflow from the eye, includes loss of trabecular cells, extracellular matrix remodeling, oxidative stress, and release of inflammatory cytokines, which are together the hallmarks of glaucoma. Although globally efficient, the topical treatments of glaucoma with eye drops containing active compounds produce, in the long-term, side effects mainly due to benzalkonium chloride, a preservative added to prevent bottle contamination. Such compound induces inflammatory processes. Thus, new data involving chemokines such as CXCL12, known to play a key role in inflammation and cellular crosstalk in the trabecular meshwork, offer new targets for the development of innovative treatments in glaucoma.
    No preview · Article · Oct 2013 · Bulletin de l'Académie nationale de médecine
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    ABSTRACT: To characterize the effects of benzalkonium chloride (BAK) in THP-1 differentiated cells in vitro. Macrophages were obtained after differentiation of THP-1 cells, a human monocytic leukemia cell line. Macrophages were exposed for 24 h to 33 nM (10(-5)%) benzalkonium chloride (BAK), 10 nM dinitrochlorobenzene (DNCB), 100 ng/mL lipopolysaccharide (LPS), 5 ng/mL tumor necrosis factor alpha (TNF-α) or phosphate buffered saline (PBS) as controls. The expression of CD11b, CD11c, CD33 and CD54 was evaluated using immunohistochemistry and flow cytometry (FCM). Phagocytosis function was analyzed using carboxylate-modified fluorescent microspheres and quantified by FCM. Migration was evaluated in cocultures with conjunctival epithelial cells. Cytokine production was detected and quantified in culture supernatants using a human cytokine array. Stimulation of THP-1-derived macrophages with a low concentration of BAK increased CD11b and CD11c expression and decreased CD33. Macrophages exposed to BAK, LPS and TNF-α had increased phagocytosis. In contrast to LPS, BAK and TNF-α increased macrophage migration. Cytokines in supernatants of macrophages exposed to BAK revealed an increased release of CCL1, CCL4/MIP-1β, TNF-α, soluble CD54/ICAM-1 and IL-1β. In vitro, BAK has a direct stimulating effect on macrophages, increasing phagocytosis, cytokine release, migration and expression of CD11b and CD11c. Long-term exposure to low concentrations of BAK should be considered as a stimulating factor responsible for inflammation through macrophage activation.
    Preview · Article · Aug 2013 · PLoS ONE
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    ABSTRACT: Chemokines - chemotactic cytokines - are small secreted proteins that attract and activate immune and non-immune cells in vitro and in vivo. It has been suggested that chemokines and their receptors play a role in the central nervous system (CNS), in addition to their well established role in the immune system. We focus here on three chemokines - CXCL12 (C-X-C motif ligand 12), CCL2 (C-C motif ligand 2), and CX3CL1 (C-X-3C motif ligand 1) - and their principal receptors - CXCR4 (C-X-C motif receptor 4), CCR2 (C-C motif receptor 2) and CX3CR1 (C-X-3C motif receptor 1), respectively. We first introduce the classification of chemokines and their G-protein coupled receptors and the main signaling pathways triggered by receptor activation. We then discuss the cellular distribution of CXCL12/CXCR4, CCL2/CCR2 and CX3CL1/CX3CR1 in adult brain and the neurotransmission and neuromodulation effects controlled by these chemokines in the adult CNS. Changes in the expression of CXCL12, CCL2 and CX3CL1 and their respective receptors are also increasingly being implicated in the pathogenesis of CNS disorders, such as Alzheimer's disease, Parkinson's disease, HIV-associated encephalopathy, stroke and multiple sclerosis, and are therefore plausible targets for future pharmacological intervention. The final section thus discusses the role of these chemokines in these pathophysiological states. In conclusion, the role of these chemokines in cellular communication may make it possible: i) to identify new pathways of neuron-neuron, glia-glia or neuron-glia communications relevant to both normal brain function and neuroinflammatory and neurodegenerative diseases; ii) to develop new therapeutic approaches for currently untreatable brain diseases.
    No preview · Article · Feb 2013 · Progress in Neurobiology
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    ABSTRACT: Methylmercury (MeHg) is a potent neurotoxin, and human beings are mainly exposed to this pollutant through fish consumption. We addressed the question of whether a diet mimicking the fish consumption of Wayanas Amerindians from French Guiana could result in observable adverse effects in mice. Wayanas adult men are subjected to a mean mercurial dose of 7 g Hg/week/kg of body weight. We decided to supplement a vegetarian-based mice diet with 0.1% of lyophilized Hoplias aimara fish, which Wayanas are fond of and equivalent to the same dose as that afflicting the Wayanas Amerindians. Total mercury contents were 1.4 ± 0.2 and 5.4 ± 0.5 ng Hg/g of food pellets for the control and aimara diets, respectively. After 14 months of exposure, the body parts and tissues displaying the highest mercury concentration on a dry weight (dw) basis were hair (733 ng/g) and kidney (511 ng/g), followed by the liver (77 ng/g). Surprisingly, despite the fact that MeHg is a neurotoxic compound, the brain accumulated low levels of mercury (35 ng/g in the cortex). The metallothionein (MT) protein concentration only increased in those tissues (kidney, muscles) in which MeHg demethylation had occurred. This can be taken as a molecular sign of divalent mercurial contamination since only Hg(2+) has been reported yet to induce MT accumulation in contaminated tissues. The suppression of the synthesis of the chemokine CCL2 in the corresponding knockout (KO) mice resulted in important changes in gene expression patterns in the liver and brain. After three months of exposure to an aimara-containing diet, eight of 10 genes selected (Sdhb, Cytb, Cox1, Sod1, Sod2, Mt2, Mdr1a and Bax) were repressed in wild-type mice liver whereas none presented a differential expression in KO Ccl2(-/-) mice. In the wild-type mice brain, six of 12 genes selected (Cytb, Cox1, Sod1, Sod2, Mdr1a and Bax) presented a stimulated expression, whereas all remained at the basal level of expression in KO Ccl2(-/-) mice. In the liver of aimara-fed mice, histological alterations were observed for an accumulated mercury concentration as low as 32 ng/g, dw, and metal deposits were observed within the cytoplasm of hepatic cells.
    Full-text · Article · Dec 2012 · International Journal of Molecular Sciences
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    Full-text · Dataset · Nov 2012
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    ABSTRACT: Purpose Blockade of the chemokine receptor CXCR3 lowers intraocular pressure and prevents retinal degeneration in an animal model of glaucoma. Methods Twenty Long-Evans male rats underwent episcleral vein cauterization in order to induce stable elevation in intraocular pressure (IOP). CXCR3 antagonist or the vehicle only were subconjunctivaly injected in glaucomatous eyes (n=10 in each), which were assessed for IOP weekly during two months. Aqueous humor outflow and trabecular filtrating function were studied using fluorophotometry and microsphere trabecular trapping respectively. Retinal nerve fiber density was quantified by scanning laser ophthalmoscopy, and optokinetic testing was performed to assess visual function. Results IOP was significantly decreased during 6 weeks in glaucomatous eyes treated with CXCR3 antagonist as compared to untreated eyes.(P
    No preview · Article · Sep 2012 · Acta ophthalmologica

  • No preview · Article · Aug 2012
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    ABSTRACT: Inappropriate expression of the chemokine CX3CL1 is reportedly known to act on inflammatory conditions in extraocular immune diseases. We studied the expression and effects of CX3CL1 in human patients, cultured human conjunctival cells, and transgenic mice exposed to benzalkonium chloride (BAC), a commonly used preservative in ophthalmic medications despite its proinflammatory properties, to determine whether CX3CL1 is involved in conjunctival inflammation. We report that CX3CL1 expression is increased in the conjunctiva of patients receiving BAC-containing medication, and correlates with clinical inflammation. BAC enhances the production of CX3CL1 in a conjunctival epithelial cell line, through the tumor-necrosis factor-α pathway, which attracts specific leukocyte subsets. In vivo, BAC-induced macrophage infiltration and subsequent inflammation of the conjunctiva is decreased in CX3CR1-deficient mice as compared with CX3CR1(+/+) controls. This translational study opens new avenue to investigate ocular surface disorders by focusing on chemokine-related inflammation and immune cell trafficking in the ocular conjunctival mucosa.
    Full-text · Article · Jun 2012 · Mucosal Immunology
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    ABSTRACT: Glaucoma, the most common cause of irreversible blindness, is a neuropathy commonly initiated by pathological ocular hypertension due to unknown mechanisms of trabecular meshwork degeneration. Current antiglaucoma therapy does not target the causal trabecular pathology, which may explain why treatment failure is often observed. Here we show that the chemokine CXCL12, its truncated form SDF-1(5-67), and the receptors CXCR4 and CXCR3 are expressed in human glaucomatous trabecular tissue and a human trabecular cell line. SDF-1(5-67) is produced under the control of matrix metallo-proteinases, TNF-α, and TGF-β2, factors known to be involved in glaucoma. CXCL12 protects in vitro trabecular cells from apoptotic death via CXCR4 whereas SDF-1(5-67) induces apoptosis through CXCR3 and caspase activation. Ocular administration of SDF-1(5-67) in the rat increases intraocular pressure. In contrast, administration of a selective CXCR3 antagonist in a rat model of ocular hypertension decreases intraocular pressure, prevents retinal neurodegeneration, and preserves visual function. The protective effect of CXCR3 antagonism is related to restoration of the trabecular function. These data demonstrate that proteolytic cleavage of CXCL12 is involved in trabecular pathophysiology, and that local administration of a selective CXCR3 antagonist may be a beneficial therapeutic strategy for treating ocular hypertension and subsequent retinal degeneration.
    Full-text · Article · Jun 2012 · PLoS ONE
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    ABSTRACT: Benzalkonium chloride (BAK), the most commonly used preservative in eye drops, is known to induce ocular irritation symptoms and dry eye in long-term treated patients and animal models. As tear film hyperosmolarity is diagnostic of some types of dry eye disease, we determined in vitro on conjunctival epithelial cells the cytoxicity of BAK in hyperosmolar conditions through cell viability, apoptosis, and oxidative stress assays. The Wong Kilbourne derivative of Chang conjunctival epithelial cells were cultured for 24 h or 48 h either in NaCl-induced hyperosmolar conditions (400-425-500 mOsM), in low concentrations of BAK (10(-4)%, 3.10(-4)%, and 5.10(-4)%), or in combination of both. We investigated cell viability through lysosomal integrity evaluation, cell death (cell membrane permeability and chromatin condensation), and oxidative stress (reactive oxygen species, superoxide anion) using spectrofluorimetry. Immunohistochemistry was performed for cytoskeleton shrinkage (phalloidin staining), mitochondrial permeability transition pore (cytochrome c release), the apoptosis effector active caspase-3, and the caspase-independent apoptosis factor AIF. We also observed early effects induced by the experimental conditions on the conjunctival cell layers using phase contrast imaging of live cells. As compared to standard culture solutions, hyperosmolar stress potentiated BAK cytotoxicity on conjunctival cells through the induction of oxidative stress; reduction of cell viability; cell membrane permeability increase; cell shrinkage with cell blebbing, as shown in phase contrast imaging of live cells; and chromatin condensation. Like BAK, but to a much lesser extent, hyperosmolarity increased cell death in a concentration-dependent manner through a caspase-dependent apoptosis characterized by a release of cytochrome c in the cytoplasm from mitochondria and the activation of caspase-3. Moreover, the caspase-independent apoptosis factor AIF was found translocated from mitochondria to the nucleus in both conditions. This study showed increased cytotoxic effects of BAK in hyperosmotic conditions, with characteristic cell death processes, namely caspase-dependent and independent apoptosis and oxidative stress. As BAK is known to disrupt tear film, which could promote evaporative dry eye and tear hyperosmolarity, BAK could promote the conditions enhancing its own cytotoxicity. This in vitro hyperosmolarity model thus highlights the risk of inducing a vicious cycle and the importance of avoiding BAK in patients with dry eye conditions.
    Full-text · Article · Apr 2012 · Molecular vision
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    ABSTRACT: Industrial pollution due to heavy metals such as mercury is a major concern for the environment and public health. Mercury, in particular methylmercury (MeHg), primarily affects brain development and neuronal activity, resulting in neurotoxic effects. Because chemokines can modulate brain functions and are involved in neuroinflammatory and neurodegenerative diseases, we tested the possibility that the neurotoxic effect of MeHg may interfere with the chemokine CCL2. We have used an original protocol in young mice using a MeHg-contaminated fish-based diet for 3 months relevant to human MeHg contamination. We observed that MeHg induced in the mice cortex a decrease in CCL2 concentrations, neuronal cell death, and microglial activation. Knock-out (KO) CCL2 mice fed with a vegetal control food already presented a decrease in cortical neuronal cell density in comparison with wild-type animals under similar diet conditions, suggesting that the presence of CCL2 is required for normal neuronal survival. Moreover, KO CCL2 mice showed a pronounced neuronal cell death in response to MeHg. Using in vitro experiments on pure rat cortical neurons in culture, we observed by blockade of the CCL2/CCR2 neurotransmission an increased neuronal cell death in response to MeHg neurotoxicity. Furthermore, we showed that sod genes are upregulated in brain of wild-type mice fed with MeHg in contrast to KO CCL2 mice and that CCL2 can blunt in vitro the decrease in glutathione levels induced by MeHg. These original findings demonstrate that CCL2 may act as a neuroprotective alarm system in brain deficits due to MeHg intoxication.
    Full-text · Article · Jan 2012 · Toxicological Sciences
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    ABSTRACT: Identification of novel molecules that can induce neuronal differentiation of embryonic stem (ES) cells is essential for deciphering the molecular mechanisms of early development and for exploring cell therapy approaches. Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) are known to be implicated early during ontogenesis in cell proliferation and neuronal differentiation. The aim of the present study was to determine the effects of VIP and PACAP on functional differentiation of ES cells. Quantitative-reverse transcription-polymerase chain reaction analysis showed an inversion of the expression pattern of PAC1 and VPAC1 receptors with time. ES cells expressed genes encoding extracellular signal-regulated kinase 1 and 2 and c-jun amino terminal kinase1. ES cells also expressed T-type α1I and α1G, L-type α1C and α1D, and N-type α1B calcium channel subunit mRNAs. Both peptides modified the shape of undifferentiated ES cells into bipolar cells expressing the neuronal marker neuron-specific enolase (NSE). Immunostaining indicated that PACAP intensified T-type α1I subunit immunoreactivity, whereas VIP increased L-types α1C and α1D, as well as N-type α1B subunit. Electrophysiological recording showed that VIP and PACAP enhanced transient calcium current. Moreover, VIP generated sustained calcium current. These findings demonstrate that PACAP and VIP induce morphological and functional differentiation of ES cells into a neuronal phenotype. Both peptides promote functional maturation of calcium channel subunits, suggesting that they can facilitate the genesis of cellular excitability.
    No preview · Article · Dec 2011 · Neuroscience
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    ABSTRACT: Purpose To characterize the phenotype, function and cytokine production of antigen presenting cells (APC) when exposed to the most common preservatives in eye drops, benzalkonium chloride (BAK).Methods APC were obtained from a human leukemia cell line THP-1. APC were exposed to 4 concentrations of BAK (10-5%, 5.10-5%, 10-4% and 5.10-4%) and PBS during 24 hours. Cellular toxicity was evaluated with an annexin V-PE/7-AAD double-staining flow cytometry analysis. Phenotype modification was evaluated by flow cytometry through a panel of cluster of differentiation: CD11b, CD11c, CD33, CD45, CD54 and CD86. Phagocytosis function was analyzed using carboxylate-modified fluorescent microspheres and quantified by flow cytometry. The cytokine production of APC exposed to BAK was measured in supernatants by a human cytokine array.Results BAK had almost no cellular toxicity at concentrations below 5.10-5%. A dose-dependent cellular toxicity of BAK was observed from 5.10-5% to 5.10-4%. At low concentrations, BAK modified the phenotype of APC with an increased expression of CD11b, CD11c, CD54 and CD86, and a decrease of CD33 and CD45. APC phagocytosis function was also increased when exposed to low concentration of BAK. Cytokines in supernatants of APC exposed to 10-5% BAK during 24 hours revealed decreased levels of IL-1β and CXCL10, and increased levels of CD40L, CXCL11, G-CSF, S-TREM-1, IL-17E, IL-6, IL-23, IL-27 and IFN-γ.Conclusion The interaction between APC and epithelial conjunctival cells are involved in iatrogenic ocular surface diseases. Low concentrations of BAK could have a stimulating effect on APC, modifying phenotype, function and cytokine production.
    No preview · Article · Sep 2011 · Acta ophthalmologica

Publication Stats

9k Citations
1,008.22 Total Impact Points


  • 2012-2015
    • French National Centre for Scientific Research
      • Institut de Chimie des Substances Naturelles
      Lutetia Parisorum, Île-de-France, France
  • 2006-2015
    • Pierre and Marie Curie University - Paris 6
      • Institut de la Vision
      Lutetia Parisorum, Île-de-France, France
  • 2011-2013
    • Polytech Paris-UPMC
      Lutetia Parisorum, Île-de-France, France
  • 2010-2012
    • Institut de la Vision
      Lutetia Parisorum, Île-de-France, France
  • 2008-2011
    • UPMC
      Pittsburgh, Pennsylvania, United States
    • University of Pittsburgh
      Pittsburgh, Pennsylvania, United States
  • 1986-2011
    • French Institute of Health and Medical Research
      • • The Vision Institute
      • • Centre de Recherche Saint Antoine U938
      Lutetia Parisorum, Île-de-France, France
  • 1984-2010
    • Unité Inserm U1077
      Caen, Lower Normandy, France
    • William Penn University
      Filadelfia, Pennsylvania, United States
  • 2007
    • Université de Rouen
      • Microbiology Signals and Microenvironment Lab (LMSM) (EA 4312)
      Mont-Saint-Aignan, Upper Normandy, France
  • 2001
    • Hôtel-Dieu de Paris – Hôpitaux universitaires Paris Centre
      Lutetia Parisorum, Île-de-France, France
    • CHNO des Quinze-Vingts
      Lutetia Parisorum, Île-de-France, France
  • 1993-1995
    • Institut Pasteur
      Lutetia Parisorum, Île-de-France, France
  • 1994
    • University of Nice-Sophia Antipolis
      • Institut de Pharmacologie Moléculaire et Cellulaire (IPMC/UMR6097 CNRS-UNS)
      Nice, Provence-Alpes-Côte d'Azur, France
  • 1992
    • McGill University
      • Department of Psychiatry
      Montréal, Quebec, Canada
  • 1989
    • Institute of Physical and Chemical Biology
      Lutetia Parisorum, Île-de-France, France
  • 1984-1986
    • The Rockefeller University
      • Laboratory of Neuroendocrinology
      New York, New York, United States