The 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: ts472@columbia.edu
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: ekunkel@bioseekinc.com
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: thomas.bieber@ukb.uni-bonn.de
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: leeyc@moak.chonbuk.ac.kr
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 Pérez Fontán 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: fontan@kids.wustl.edu
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: nicholas.shworak@dartmouth.edu
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: jweitz@thrombosis.hhscr.org
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: mpollak@rics.bwh.harvard.edu
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: quarl001@mc.duke.edu
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: raisz@nso.uchc.edu
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: ellisond@ohsu.edu
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: bernard.rossier@ipharm.unil.ch
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: gmorreale@iib.uam.es
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: tzoeller@bio.umass.edu
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: jensen.michael@mayo.edu
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: j-sznajder@northwestern.edu
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: pkubes@ucalgary.ca
View the PDF of this article at:
https://www.the-jci.org/press/16510.pdf
Journal
Journal of Clinical Investigation