
April 2003 From Journal of Clinical Investigation JCI Table of Contents, April 1, 2003The Latest RAGE in Restinosis Expansion of the neointima is a problem in chronic atherosclerosis as well as in response to acute arterial injury. Smooth muscle cells (SMCs) play a key role in the pathologic extension of the neointima that ultimately impinges on the vascular lumen. RAGE, the receptor for advanced glycation end products, is upregulated at sites of vascular pathology, and its blockage is beneficial in mouse atherosclerosis models. Yoshifumi Naka and colleagues have examined RAGE's role in acute arterial injury. As they report (pages 959�972), inhibition of RAGE suppressed neointimal formation in mice upon arterial injury and decreased SMC proliferation, migration, and expression of ECM proteins. Inhibition of RAGE specifically in SMCs yielded similar results. The data point to a key role for RAGE in regulating SMCs after arterial injury and suggest the receptor as a target for therapeutic intervention in heart disease. CONTACT: Taichi Sakaguchi Columbia University New York, NY 10032 USA Phone: 1-212-305-0211 Fax: 1-212-305-5337 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/17115.pdf Spreading Mucosal Immunity Local mucosal immunization leads to antigen-specific IgA production at distant mucosal sites, presumably through the migration of activated B cells. Because of the important implications for vaccine development, Eric Kunkel and colleagues are working to understand the mechanisms of IgA-secreting B cell trafficking between distant mucosal sites. Having previously identified a chemokine called MEC, which is expressed by epithelial cells in a variety of mucosal tissues, they report now (pages 1001�1010) that the MEC-binding chemokine receptor CCR10 is expressed on IgA-secreting B cells. This suggests that interaction between CCR10 and its mucosal epithelial ligand MEC may form the basis for a homing mechanism that guides the specific dissemination of IgA-secreting B cells after local immunization. CONTACT: Eric Kunkel Bioseek, Inc. 863-C Mitten Rd. Burlingame, CA 94010 USA Phone 1-650-231-1251 Fax 1-650-552-0725 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/17244.pdf Atopy-Promoting Dendritic Cells The gamma chain of the high-affinity IgE receptor (FceRIgamma) is selectively expressed on antigen-presenting cells from atopic individuals and has been implicated in the pathophysiology of atopic diseases. Interested in the regulation of this receptor on DCs, Thomas Bieber and colleagues have examined the expression of the different components of the receptor during DC maturation (pages 1047�1056). While FceRIapha is present at high levels throughout DC development in atopic and nonatopic individuals, expression of FceRIgamma, which is essential for surface expression of the multimeric receptor, is normally downregulated upon DC differentiation. DCs from atopic individuals, however, show significant levels of FceRIgamma expression, and express the receptor on the surface of mature DCs. In addition to established anti-IgE treatments, modulation of FceRIgamma expression in DCs might prove useful in the management of atopic diseases. CONTACT: Thomas Bieber University of Bonn Department of Dermatology Sigmund Freud Str. 25 53105 Bonn, GERMANY Phone: 1-49-228-287-4388 Fax: 1-49-228-287-4881 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/15932.pdf PTEN: A New Player in Allergen-Induced Inflammation Eosinophil accumulation and activation are important events in the development of asthma and involve the enzyme PI3K. The phosphatase PTEN, a major player in cell survival signaling, is known to oppose the action of PI3K. Interested in the role of PTEN in bronchial asthma, Yong Lee and colleagues studied the effects of PI3K inhibitors and PTEN in a mouse model of allergen-induced bronchial inflammation and airway hyperresponsiveness. On pages 1083�1092 the authors show that PTEN expression is diminished in airway epithelial cells of antigen-sensitized and -challenged mice. Intratracheal administration of PI3K inhibitors or adenovirus carrying PTEN cDNA remarkably reduced eosinophil levels and inflammation. One likely mechanism for this reduction is PTEN-mediated eosinophil degranulation and suppression of IL-4 and IL-5. The data support the potential use of PTEN or other PI3K inhibitors for the regulation of allergic inflammation. CONTACT: Yong Chul Lee Chonbuk National University Medical School Department of Internal Medicine 634-18 Keumamdong Chonju 561-712, KOREA Phone: 1-8263-250-1664 Fax: 1-8263-254-1609 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/16440.pdf Neuronal and Inflammatory Cell Interplay During Lung Injury Neurogenic inflammation -- the initiation or amplification of the inflammatory response to noxious stimuli by injured or irritated sensory nerves -- is mediated by PPT-A gene�encoded neurokinins stored primarily in unmyelinated nerve fibers. Recent reports have also indicated the presence of PPT-A mRNA and neurokinin-like immunoreactivity in airway neurons and inflammatory cells. Interested in the interaction between these two cellular reservoirs of neurokinins in the lung, J. Julio P�rez Font�n and colleagues examined their role in protection against both immune-complex�mediated and mechanical lung injury in a murine model (pages 973�980). The data revealed that the PPT-A gene must be functional in both sensory nerves and hematopoietic cells to propagate neurogenic inflammation and injury in the lung -- an unexpected synergy between sensory nerve fibers and PPT-A gene�expressing inflammatory cells. CONTACT: J. Julio Perez Fontan Washington University School of Medicine St. Louis Children's Hospital Department of Pediatrics One Children's Place St. Louis, MO 63110 USA Phone: 1-314-454-2527 Fax: 1-314-361-0733 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/17458.pdf Normal Levels of Anticoagulant Heparan Sulfate are not Essential for Normal Hemostasis. CONTACT: Nicholas Shworak Dartmouth Medical School Borwell 540, HB7504 Dartmouth Hitchcock Medical Center One Medical Center Drive Lebanon, NH 03756 USA Phone: 1-603-650-6401 Fax: 1-603-653-0510 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/15809.pdf ACCOMPANYING COMMENTARY: Heparan sulfate: antithrombotic or not? CONTACT: Jeffrey I. Weitz Hamilton Civic Hospitals Research Centre 711 Concession Street Hamilton, Ontario, L8V 1C3 CANADA Phone: 1-905-574-8550 Fax: 1-905-575-2646 E-mail: [email protected] View the PDF of this commentary at: https://www.the-jci.org/press/18234.pdf The Calcium-Sensing Receptor is Required for Normal Calcium Homeostasis Independent of Parathyroid Hormone CONTACT: Martin Pollack Brigham And Women's Hospital 77 Avenue Louis Pasteur Boston, MA 02115-5727 USA Phone: 1-617-525-5840 Fax: 1-617-525-5841 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/17416.pdf RELATED ARTICLE: Rescue of the Skeletal Phenotype in CasR-Deficient Mice by Transfer onto the Gcm2 Null Background CONTACT: Darryl L. Quarles Duke University Medical Center Department of Medicine P.O. Box 3036, DUMC Durham, NC 27710 USA Phone: 1-919-660-6853 Fax: 1-919-684-4476 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/17054.pdf ACCOMPANYING COMMENTARY ON BOTH ARTICLES: The hunting of the snark: the elusive calcium receptor(s) CONTACT: Lawrence G. Raisz Univ. Of Connecticut Health Center Dept. Of Medicine General Clinical Research Center mail code #3805 263 Farmington Avenue Farmington, CT 06032 USA Phone: 1-860-679-2129 Fax: 1-860-679-1258 E-mail: [email protected] View the PDF of this commentary at: https://www.the-jci.org/press/18235.pdf WNK Kinases Regulate Thiazide-Sensitive Na-Cl Cotransport CONTACT: David H. Ellison Oregon Health Sciences University Nephrology/Suite 262 3314 SW US Veterans Hospital Rd Portland, OR 97201 USA Phone: 1-503-494-8490 Fax: 1-503-494-5330 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/17443.pdf ACCOMPANYING COMMENTARY: Negative Regulators of Sodium Transport in the kidney: Key Factors in Understanding Salt-Sensitive Hypertension? CONTACT: Bernard C. Rossier Institut de Pharmacologie et de Toxicologie de L'Universite Rue Du Bugnon 27 Lausanne, Lausanne CH-1005 CH-1005 SWITZERLAND Phone: 1 +41-21-6925351 Fax: 1 +41-21-6925355 E-mail: [email protected] View the PDF of this commentary at: https://www.the-jci.org/press/18232.pdf Early Maternal Hypothyroxinemia Alters Histogenesis and Cerebral Cortex Cytoarchitecture of the Progeny. CONTACT: Gabriella Morreale de Escobar Universidad Autonoma de Madrid Instituto de Investigacione Biomedicas Alberto Sol Arturo Duperier, 4 28029-Madrid, SPAIN Phone: 1-34-91-397-54-00 Fax: 1-34-91-585-45-87 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/16262.pdf ACCOMPANYING COMMENTARY: Transplacental Thyroxine and Fetal Brain Development CONTACT: Thomas R. Zoeller University of Massachussetts Biology Department and Molecular and Cellular Biology Program Morrill Science Center Amherst, MA 01300 USA Phone: 1-413-545-2088 Fax: 1-413-545-3243 E-mail: [email protected] View the PDF of this commentary at: https://www.the-jci.org/press/18236.pdf Energy Expenditure, Sex and Endogenous Fuel Availability in Humans CONTACT: Michael D. Jensen Endocrine Research Unit Mayo Clinic, 5-164 West Joseph 200 First Street, SW Rochester, MN 55905 USA Phone: 1-507-255-6449 Fax: 1-507-255-4828 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/16253.pdf Hypoxia-Induced Endocytosis of Na,K-ATPase in Alveolar Epithelial Cells is Mediated by Mitochondrial Reactive Oxygen Species and PKC-Zeta CONTACT: J.I. Sznajder Northwestern University Pulmonary and Critical Care Medicine 300 E. Superior St. Tarry Bldg. 14-707 Chicago, IL 60611 USA Phone: 1-312-503-1637 Fax: 1-312-908-4650 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/16826.pdf Endothelial-derived TLR4: the key molecule in LPS-induced neutrophil sequestration in to the lungs CONTACT: Paul Kubes University of Calgary Department of Physiology and Biophysics 3330 Hospital Drive NW Calgary, Alberta T2N 4N1 CANADA Phone: 1-403-220-8558 Fax: 1-403-283-1267 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/16510.pdf |