Article
Microbiology
Inge M. N. Wortel, Seonyoung Kim, Annie Y. Liu, Enid C. Ibarra, Mark J. Miller
Summary: Listeria monocytogenes (Lm) is a food-borne pathogen that causes severe bacterial gastroenteritis. The motility of Lm plays an important role in locating and engaging target cells for invasion, enhancing invasion efficiency. Lm motility also affects interactions with host cellular immunity.
Article
Biochemistry & Molecular Biology
Mitali Das, Sujay Subbayya Ithychanda, Edward F. Plow
Summary: Plasminogen and its receptors, including histone 2B (H2B), play important roles in the responses of various cell types. This study investigated the involvement of H2B in plasminogen-induced endothelial cell migration. The results showed that H2B is present on viable endothelial cells and its antibody blockade inhibited plasminogen-dependent migration. Furthermore, H2B was found to interact with PAR1 and PAR2, suggesting a mechanism for linking plasminogen to wound healing and angiogenesis.
Article
Gastroenterology & Hepatology
Jean-Paul Motta, Simone Palese, Carmine Giorgio, Kevin Chapman, Alexandre Denadai-Souza, Perrine Rousset, David Sagnat, Laura Guiraud, Anissa Edir, Carine Seguy, Laurent Alric, Delphine Bonnet, Barbara Bournet, Louis Buscail, Cyrielle Gilletta, Andre G. Buret, John L. Wallace, Morley D. Hollenberg, Eric Oswald, Elisabetta Barocelli, Sylvie Le Grand, Bruno Le Grand, Celine Deraison, Nathalie Vergnolle
Summary: Elevated thrombin activity in the colon of Crohn's disease patients may lead to tissue damage and inflammation. Experimental evidence suggests that colonic thrombin and protease-activated receptor-1 could be potential mechanisms involved in mucosal damage and loss of function.
JOURNAL OF CROHNS & COLITIS
(2021)
Article
Cell Biology
Ian M. Cartwright, Alexander S. Dowdell, Camila Hanson, Rachael E. Kostelecky, Nichole Welch, Calen A. Steiner, Sean P. Colgan
Summary: This study explores the mechanisms of inflammatory acidification caused by PMN-IEC interactions, and finds that the acidification response is related to the number and direction of PMNs, as well as the reactive oxygen species generated during PMN TEM.
JOURNAL OF LEUKOCYTE BIOLOGY
(2022)
Article
Cell Biology
Shuhua Luo, Chaoxiong Liao, Lina Zhang, Chunxiu Ling, Xuedi Zhang, Pengyun Xie, Guomei Su, Zhanghui Chen, Liangqing Zhang, Tianwen Lai, Jing Tang
Summary: N6-methyladenosine (m6A) modification is the most prevalent mRNA internal modification and serves as a widespread regulatory mechanism in various physiological processes. In this study, we found that methyltransferase-like protein 3 (METTL3) plays a crucial role in neutrophil activation. METTL3 controls the release of neutrophils from the bone marrow to circulation by regulating the surface expression of CXC chemokine receptor 2 (CXCR2) through Toll-like receptor 4 (TLR4) signaling in lipopolysaccharide (LPS)-induced endotoxemia. We discovered that the mRNA of TLR4 is modified by m6A, resulting in increased translation and decreased degradation, leading to elevated levels of TLR4 protein and subsequent activation of TLR4 signaling in neutrophils. The downregulation of TLR4 expression reduces cytokine secretion in METTL3-deleted neutrophils upon LPS stimulation through the TLR4/Myd88/nuclear factor KB (NF-KB) signaling pathway. Overall, these findings demonstrate that METTL3-mediated TLR4 expression is a critical determinant of neutrophil activation in endotoxemia.
Article
Biochemistry & Molecular Biology
Abderrahim Nemmar, Marc F. Hoylaerts
Summary: Inhalation of particulate matter in polluted air can cause lung inflammation, platelet activation, and cardiovascular complications. Neutrophil enzymes release ADP and sensitize platelets, amplifying their contribution to the complications induced by ambient particle inhalation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Louise Hulme, Alexandra Hochstetler, Christian Schwerk, Horst Schroten, Hiroshi Ishikawa, Chun -Yu Tung, Benjamin Perrin, Bonnie Blazer-Yost
Summary: The objective of this study was to characterize the HIBCPP cell line as a model of the BCSFB and to explore the signaling pathways associated with TRPV4 channel activation using electrophysiology. RT-PCR was used to determine gene expression, and microscopy techniques were used to examine cell morphology and transporter localization. The study found that TRPV4 activation resulted in changes in ion flux and fluid secretion, which were modulated by several effectors. The HIBCPP cell line can be used for studying transporter function, intracellular signaling, and regulation of CSF production.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Medicine, Research & Experimental
Lingjun Zhang, Nozha Borjini, Yu Lun, Sweta Parab, Gospel Asonye, Rupesh Singh, Brent A. Bell, Vera L. Bonilha, Andrei Ivanov, David A. Fox, Rachel Caspi, Feng Lin
Summary: CDCP1, highly expressed on the surface of cancer cells, was found to be present on retinal pigment epithelial (RPE) cells. It interacts with CD6 on T cells, inducing cytoskeleton remodeling and focal adhesion disruption in RPE cells, leading to the development of autoimmune uveitis.
Article
Multidisciplinary Sciences
Sladjana Skopelja-Gardner, Joyce Tai, Xizhang Sun, Lena Tanaka, James A. Kuchenbecker, Jessica M. Snyder, Paul Kubes, Tomas Mustelin, Keith B. Elkon
Summary: Exposure to UV light triggers a neutrophil-dependent injury response in the kidney, leading to subclinical renal inflammation and injury. Neutrophils not only migrate to the skin but also to the kidney post UV light exposure, contributing to the renal induction of inflammation and injury genes. Patients with lupus have blood neutrophils similar to those observed in mice post-UV exposure, suggesting a potential role of these cells in mediating inflammation and injury.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cell Biology
Ruth A. Houseright, Veronika Miskolci, Oscar Mulvaney, Valeriu Bortnov, Deane F. Mosher, Julie Rindy, David A. Bennin, Anna Huttenlocher
Summary: MYDGF, induced by tissue damage, regulates neutrophil motility to damaged tissues through the HIF-1α pathway. Depletion of MYDGF impairs wound healing and inflammation resolution, while persistent neutrophil inflammation in MYDGF mutants is dependent on HIF-1α pathway.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Gastroenterology & Hepatology
Ying Xie, Lindsey Fontenot, Andrea Chupina Estrada, Becca Nelson, Jiani Wang, David Q. Shih, Wendy Ho, S. Anjani Mattai, Florian Rieder, Dane D. Jensen, Nigel W. Bunnett, Hon Wai Koon
Summary: The study demonstrates that Elafin can suppress collagen synthesis in intestinal fibroblasts by inhibiting protease-activated receptor 2, which is dependent on cathelin S, leading to a reduction in intestinal fibrosis.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Article
Cell Biology
Rouven Schoppmeyer, Abraham C. van Steen, Lanette Kempers, Anne L. Timmerman, Martijn A. Nolte, Pleun Hombrink, Jaap D. van Buul
Summary: This study investigates how cytotoxic T lymphocytes (CTLs) efficiently leave the circulation to target cancer cells or contribute to inflammation by crossing the endothelium. The researchers found that human central memory CTLs predominantly cross the endothelium in a paracellular fashion, while effector and effector memory CTLs preferentially cross in a transcellular fashion. The study also reveals the mechanism of CTL-endothelium interaction and the involvement of ICAM-1 and CX3CL1:CX3CR1 in transcellular migration.
Article
Ophthalmology
Yong Lin, Qi Liu, Li Li, Rusen Yang, Juxiu Ye, Shuai Yang, Guangying Luo, Peter S. Reinach, Dongsheng Yan
Summary: The study reveals the critical role of SIRT1 in controlling corneal epithelial wound healing (CEWH). Upregulation of SIRT1 and its modification of cortactin promote corneal epithelial cell migration by increasing lamellipodia development at the wound edge, which may serve as a potential target for enhancing CEWH.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
Article
Immunology
Pingchuan Wang, Tianming Li, Changping Niu, Siyu Sun, Dongyan Liu
Summary: ROS generated by prolonged hyperoxia therapy can damage the intestinal barrier, impairing intestinal growth and development and promoting intestinal diseases. This study investigated the molecular mechanisms of the neonate intestinal response to ROS and identified potential targets for preventing intestinal barrier damage.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Immunology
Chendi Jing, Chenghua Liu, Yu Liu, Ruli Feng, Run Cao, Zhangchun Guan, Bo Xuan, Yaping Gao, Qi Wang, Nana Yang, Yuanfang Ma, Lefu Lan, Jiannan Feng, Beifen Shen, Hui Wang, Yanyan Yu, Guang Yang
Summary: The alkaline protease (AprA) secreted by Pseudomonas aeruginosa may aggravate infection by destroying formed NETs, an effect further enhanced by its antibodies. AprA degrades NET components, but does not affect NET formation.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cell & Tissue Engineering
Eloise Mussard, Cecile Pouzet, Virginie Helies, Geraldine Pascal, Sandra Fourre, Claire Cherbuy, Aude Rubio, Nathalie Vergnolle, Sylvie Combes, Martin Beaumont
STEM CELL RESEARCH
(2020)
Article
Pharmacology & Pharmacy
Celine Auge, Xavier Game, Nathalie Vergnolle, Philippe Lluel, Sophie Chabot
FRONTIERS IN PHARMACOLOGY
(2020)
Article
Gastroenterology & Hepatology
Jean-Paul Motta, Simone Palese, Carmine Giorgio, Kevin Chapman, Alexandre Denadai-Souza, Perrine Rousset, David Sagnat, Laura Guiraud, Anissa Edir, Carine Seguy, Laurent Alric, Delphine Bonnet, Barbara Bournet, Louis Buscail, Cyrielle Gilletta, Andre G. Buret, John L. Wallace, Morley D. Hollenberg, Eric Oswald, Elisabetta Barocelli, Sylvie Le Grand, Bruno Le Grand, Celine Deraison, Nathalie Vergnolle
Summary: Elevated thrombin activity in the colon of Crohn's disease patients may lead to tissue damage and inflammation. Experimental evidence suggests that colonic thrombin and protease-activated receptor-1 could be potential mechanisms involved in mucosal damage and loss of function.
JOURNAL OF CROHNS & COLITIS
(2021)
Review
Cell Biology
Claire Racaud-Sultan, Nathalie Vergnolle
Summary: In adult stem cells, GSK3 beta plays a crucial role in regulating cell survival, proliferation, adherence, and differentiation, with its activity dependent on integrin and PAR engagement. Prolonged activation of GSK3 beta may lead to defects in epithelial regeneration and resistance to chemotherapy in leukemic cells, with a sexual dimorphism in GSK3 beta-dependent cellular functions. Adjusted therapy based on GSK3 beta activity is essential for inflammatory and cancer diseases in patients.
Article
Gastroenterology & Hepatology
Matthieu Rouland, Lucie Beaudoin, Ophelie Rouxel, Leo Bertrand, Lucie Cagninacci, Azadeh Saffarian, Thierry Pedron, Dalale Gueddouri, Sandra Guilmeau, Anne-Francoise Burnol, Latif Rachdi, Asmaa Tazi, Juliette Mouries, Maria Rescigno, Nathalie Vergnolle, Philippe Sansonetti, Ute Christine Rogner, Agnes Lehuen
Summary: Our study found in autoimmune T1D models a consistent decrease in IL-17A, IL-22, and IL-23A in gut mucosa, along with impaired intestinal epithelial cell function and compromised gut integrity. This was accompanied by dysbiosis, including progressive loss of SFB. Anti-inflammatory treatment restored gut mucosa and immune cell function, reducing diabetes incidence.
Article
Gastroenterology & Hepatology
Nuria Sola Tapias, Alexandre Denadai-Souza, Claire Rolland-Fourcade, Muriel Quaranta-Nicaise, Catherine Blanpied, Marlene Marcellin, Anissa Edir, Corinne Rolland, Carla Cirillo, Gilles Dietrich, Laurent Alric, Guillaume Portier, Sylvain Kirzin, Delphine Bonnet, Emmanuel Mas, Odile Burlet-Schiltz, Celine Deraison, Chrystelle Bonnart, Nathalie Vergnolle, Frederick Barreau
Summary: Inflammatory bowel disease patients exhibit excessive induction of endoplasmic reticulum stress in intestinal epithelial cells, which is associated with increased serine protease activity. The increased trypsin activity induced by ER stress destabilizes intestinal barrier function and promotes the development of inflammatory processes by controlling inflammatory mediators, dependent on the activation of protease-activated receptors 2 and 4.
JOURNAL OF CROHNS & COLITIS
(2021)
Article
Immunology
Jean-Paul Motta, Corinne Rolland, Anissa Edir, Ana-Carolina Florence, David Sagnat, Chrystelle Bonnart, Perrine Rousset, Laura Guiraud, Muriel Quaranta-Nicaise, Emmanuel Mas, Delphine Bonnet, Elena F. Verdu, Derek M. McKay, Etienne Buscail, Laurent Alric, Nathalie Vergnolle, Celine Deraison
Summary: Imbalance between proteases and their inhibitors is crucial in the development of Inflammatory Bowel Diseases (IBD). This study identifies a previously unrevealed production of elastase 2A (ELA2A) by colonic epithelial cells in IBD patients, leading to inflammation and loss of barrier function. Targeting ELA2A hyperactivity could be a potential treatment for IBD.
MUCOSAL IMMUNOLOGY
(2021)
Review
Gastroenterology & Hepatology
Jean-Paul Motta, John L. Wallace, Andre G. Buret, Celine Deraison, Nathalie Vergnolle
Summary: This article discusses the natural organization of microorganisms on gastrointestinal surfaces, microbiota taxonomy, biogeographical localization, and trans-kingdom interactions within the biofilm habitat. The importance of the host-biofilm relationship in gut homeostasis and disease is evaluated, along with the role of biofilms in gut homeostasis and pathological processes. Further research on biofilm properties and communication could provide insights into gut physiology and potential therapeutic options for gastrointestinal diseases.
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY
(2021)
Article
Gastroenterology & Hepatology
Jean-Paul Motta, Celine Deraison, Sylvie Le Grand, Bruno Le Grand, Nathalie Vergnolle
Summary: A new paradigm has been proposed for the treatment of inflammatory bowel diseases, focusing on tissue repair and mucosal healing in addition to resolving symptoms and inflammation. The PAR-1 antagonist has shown potential benefits in promoting mucosal repair in Crohn's disease patients, suggesting a new indication for IBD treatment.
INFLAMMATORY BOWEL DISEASES
(2021)
Editorial Material
Gastroenterology & Hepatology
Nathalie Vergnolle
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY
(2022)
Article
Gastroenterology & Hepatology
Mathieu Berger, Laura Guiraud, Alexia Dumas, David Sagnat, Gaelle Payros, Corinne Rolland, Nathalie Vergnolle, Eline Deraison, Nicolas Cenac, Claire Racaud-Sultan
Summary: Prenatal stress negatively impacts the proliferation and differentiation of intestinal stem cells and progenitors. This effect is mediated by the activation of protease-activated receptor 2 (PAR2) and muscarinic receptor 3 (M3) in a sexually dimorphic manner. In males, prenatal stress reinforces the negative control on cell proliferation and differentiation, while in females, it induces a switch in regulation leading to a resistant and proliferative phenotype of progenitors.
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
(2022)
Review
Pharmacology & Pharmacy
Celine Deraison, Chrystelle Bonnart, Philippe Langella, Karine Roget, Nathalie Vergnolle
Summary: Elafin and its precursor trappin-2 play an important role in protecting the intestinal mucosal barrier from microbial invasion, especially in gut inflammation. They have shown protective effects in gut intestinal disorders associated with acute or chronic inflammation, as well as gluten sensitization disorders, through various mechanisms. The potential therapeutic application of delivering trappin-2/elafin to the intestinal mucosa surface and its role in intestinal tissue repair are also discussed.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Geriatrics & Gerontology
Y. Santin, S. Lopez, I Ader, S. Andrieu, N. Blanchard, A. Carriere, L. Casteilla, B. Cousin, N. Davezac, P. De Souto Barreto, C. Dray, N. Fazilleau, D. Gonzalez-Dunia, P. Gourdy, S. Guyonnet, N. Jabrane-Ferrat, O. Kunduzova, F. Lezoualc'h, R. Liblau, L. O. Martinez, C. Moro, P. Payoux, L. Penicaud, V Planat-Benard, C. Rampon, Y. Rolland, J-P Schanstra, F. Sierra, P. Valet, A. Varin, N. Vergnolle, B. Vellas, J. Vina, B. P. Guiard, A. Parini
Summary: Aging is a major risk factor for chronic diseases, and efforts are now focused on promoting healthy aging by identifying early biological markers associated with functional status. The INSPIRE program aims to discover mechanisms of accelerated aging and predict frailty and pathological aging using a cohort of SWISS mice. This comprehensive study will provide valuable insights into the role of dietary and exercise interventions in influencing the rate of biological aging and identifying targets for healthy aging promotion.
JOURNAL OF FRAILTY & AGING
(2021)
Article
Geriatrics & Gerontology
S. Guyonnet, Y. Rolland, C. Takeda, P-J Ousset, I Ader, N. Davezac, C. Dray, N. Fazilleau, P. Gourdy, R. Liblau, A. Parini, P. Payoux, L. Penicaud, C. Rampon, P. Valet, N. Vergnolle, S. Andrieu, P. De Souto Barreto, L. Casteilla, B. Vellas
Summary: The INSPIRE initiative aims to establish a research program focusing on the biological mechanisms of aging and healthy aging, from animal models to humans and the healthcare system. The INSPIRE-T cohort gathers diverse data from individuals of different ages and functional capacities, with the goal of identifying markers of aging and age-related diseases for potential therapeutic targeting.
JOURNAL OF FRAILTY & AGING
(2021)
Article
Geriatrics & Gerontology
P. De Souto Barreto, S. Guyonnet, I Ader, S. Andrieu, L. Casteilla, N. Davezac, C. Dray, N. Fazilleau, P. Gourdy, R. Liblau, A. Parini, P. Payoux, L. Penicaud, C. Rampon, Y. Rolland, P. Valets, N. Vergnolle, B. Vellas
Summary: Aging is a key risk factor for chronic diseases and functional decline, and understanding the interplay between biological aging, disease biology, and a function-centered care approach is crucial for preventive strategies. The INSPIRE research program aims to explore how manipulation of biological aging and implementation of function-centered care pathways can contribute to healthy aging trajectories.
JOURNAL OF FRAILTY & AGING
(2021)