|
Inflammation & Allergy -
Drug Targets
(Formerly 'Current Drug Targets - Inflammation & Allergy')
ISSN: 1871-5281
Inflammation & Allergy
- Drug Targets
Volume 6, Number 3, September 2007
Contents
B Cells and Beyond: Therapeutic Opportunities Targeting
Inflammation Pp. 142-149
Bailin Liang, Ashlyn Eaton-Bassiri and Peter J. Bugelski
[Abstract]
Exhaled Breath Biomarkers in Asthmatic Children
Pp. 150-159
Massimo Corradi, Chiara Zinelli and Carlo Caffarelli
[Abstract]
Microbial Immune Evasion Employing Suppressor of Cytokine
Signaling (SOCS) Proteins Pp. 160-167
Andrea Baetz, Stefan Zimmermann and Alexander H. Dalpke
[Abstract]
Anti-Inflammatory Responses of Resveratrol
Pp. 168-173
Samarjit Das and Dipak K. Das
[Abstract]
Dehydroepiandrosterone Delays LDL Oxidation In
Vitro and Attenuates Several oxLDL-Induced Inflammatory
Responses in Endothelial Cells Pp. 174-182
Rebeca López-Marure, Claudia Huesca-Gómez,
María de Jesús Ibarra-Sánchez, Alejandro
Zentella and Oscar Pérez-Méndez
[Abstract]
Macrophage Migration Inhibitory Factor: A Therapeutic
Target Across Inflammatory Diseases Pp. 183-190
Alberta Y. Hoi, Magdy N. Iskander and Eric F. Morand
[Abstract]
Abstracts
[Back to top]
B Cells and Beyond: Therapeutic Opportunities
Targeting Inflammation
Bailin Liang, Ashlyn Eaton-Bassiri and Peter J. Bugelski
Classically, B-lymphocytes (B cells) are considered to be
the mediators of humoral immunity and their role in inflammatory
disease largely confined to the down-stream function of antigen-antibody
complexes, e.g., in fixing complement and mediating antibody
dependent cellular cytotoxicity. More recently, and with the
growing acceptance of the view that the immune system operates
as an interconnected web of cells and cytokines, a larger
role for B cells has been proposed. In this review, with a
focus on how B cells and their cytokine products may present
novel therapeutic targets, we will briefly discuss B cell
ontogeny and discuss the evidence supporting a larger role
for B cells in a variety of inflammatory diseases. Special
emphasis will be placed on autoimmune diseases. These discussions
are intended to provide the reader with the basis for viewing
B cells as players of a broader role in inflammatory disease
and thus suggest avenues for exploiting B cell directed therapy
in novel ways.
[Back to top]
Exhaled Breath Biomarkers in Asthmatic Children
Massimo Corradi, Chiara Zinelli and Carlo Caffarelli
Asthma is a chronic inflammatory disease of the airways which
affects about 10-25% of children in Western countries. Monitoring
of inflammation is considered an important tool in the diagnosis
and follow-up of asthma, including assessment of severity
and response to treatment. Bronchial biopsy specimens and
bronchoalveolar lavage are reliable ways to assess airway
inflammation. However, such invasive procedures are not feasible
for repetitive measurements. In clinical practice, correlation
of symptom scores and measurement of lung function with airway
inflammation may be poor. Bronchial hyperresponsiveness to
metacholine and induced sputum are time-consuming, difficult
to perform before adolescence and can not be measured serially.
Therefore, the greatest interest has recently been directed
towards alternative approaches to determine markers involved
in the inflammatory reaction. In childhood, such approaches
must be non-invasive, reproducible and easy to perform. Furthermore,
the inflammatory markers should accurately measure not only
the degree of inflammation but also changes depending upon
treatment or allergen exposure. Recently, the measurements
of inflammatory markers in both exhaled breath and condensate
have emerged as a possible non invasive method in the assessment
of airway inflammation.
[Back to top]
Microbial Immune Evasion Employing Suppressor of Cytokine
Signaling (SOCS) Proteins
Andrea Baetz, Stefan Zimmermann and Alexander H. Dalpke
Cytokines mediate communication between cells of the immune
system and are of crucial importance to induce an appropriately
regulated immune response to invading pathogens. Cytokine
receptor signaling has to be tightly controlled to balance
anti-microbial and tissue-destructive effects, both of which
are inherently associated with cytokine-mediated inflammation.
Suppressor of cytokine signaling (SOCS) proteins have been
identified as intracellular, inducible feedback inhibitors
which limit the signal magnitude of cytokines employing Janus
kinase (Jak) and signal transducer and activator of transcription
(STAT) pathways. Interfering with cytokine receptor signaling
has been shown to be a promising strategy used by various
microbial pathogens to evade otherwise detrimental immune
responses. To this, microbes make use of a variety of different
means. Recent reports now indicate that certain bacteria,
viruses and parasites have also learned to use the host’s
inhibitory SOCS proteins for manipulating cytokine receptor
signaling, especially to circumvent the actions of interferon.
Progress in the field of microbial immune evasion mediated
by SOCS proteins is discussed in this review. Modulating the
host’s SOCS system therefore could also be a promising
new approach for molecular therapeutic strategies.
[Back to top]
Anti-Inflammatory Responses of Resveratrol
Samarjit Das and Dipak K. Das
Resveratrol (trans-3,4’,5-trihydroxystilbene), a natural
polyphenolic, non-flavonoid antioxidant, is a phytoalexin
found in many plants including grapes, nuts and berries. Recent
studies have documented that resveratrol has various health
benefits, such as cardiovascular and cancer preventive properties.
However, the experimental basis for such health benefit is
not fully understood. One of the possible mechanisms for its
protective activities is by down regulation of the inflammatory
responses. That includes the inhibition of synthesis and release
of pro-inflammatory mediators, modifications of eicosanoid
synthesis, inhibition of some activated immune cells, or inhibiting
the enzymes, such as cyclooxy-genase-1 (COX-1) or cyclooxygenase-2
(COX-2), which are responsible for the synthesis of pro-inflammatory
mediators through the inhibitory effect of resveratrol on
transcription factors like nuclear factor κB
(NFκB)
or activator protein-1 (AP-1). Being a phenolic compound,
resveratrol certainly possesses a low bioavailability and
most importantly, a rapid clearance from the plasma. Recent
growing interest in varying protective nature of resveratrol
may clinically also hold a respectable position as a better
alternative for anti-inflammatory drugs. The purpose of this
review is to provide evidence that resveratrol exhibits potent
anti-inflammatory activity and also to explain the underling
mechanism for both resveratrol- induced cardioprotective and
anti-inflammatory properties. While it is true that the cardioprotective
properties of resveratrol are likely attributable, at least
in part, to its anti-inflammatory properties, the mechanisms
discussed address foremost mechanisms for the anti-inflammatory
activity which, in turn, is responsible for cardioprotection.
[Back to top]
Dehydroepiandrosterone Delays LDL Oxidation In
Vitro and Attenuates Several oxLDL-Induced Inflammatory
Responses in Endothelial Cells
Rebeca López-Marure, Claudia Huesca-Gómez,
María de Jesús Ibarra-Sánchez, Alejandro
Zentella and Oscar Pérez-Méndez
Dehydroepiandrosterone (DHEA) has a protective role against
atherosclerosis, most likely mediating an anti-inflammatory
action. In order to understand the mechanisms involved in
this protection, we evaluated the effects of DHEA on several
molecules involved in the inflammatory response. Reactive
oxygen species (ROS), expression of adhesion molecules, activation
of the NF-κB/IκB-α
pathway and of the AP-1 transcription factor were evaluated
in human umbilical vein endothelial cells (HUVECs) treated
with oxidized low density lipoproteins (oxLDL) and DHEA. We
also determined if DHEA affected LDL oxidation in vitro.
100 μM
DHEA-treatment inhibited the oxLDL-induced expression of ICAM-1,
VCAM-1, PECAM-1, ROS production, and U937 cells adhesion to
HUVECs. DHEA also delayed the kinetics of LDL oxidation in
vitro. While DHEA did not affect the translocation of
NF-κB
neither the degradation IκB-α,
it led to an increased translocation of AP-1. Our results
suggest that DHEA inhibits the expression of molecules involved
in the inflammatory process in endothelial cells activated
with oxLDL, therefore its potential anti-inflammatory properties
should be evaluated for the treatment of chronic inflammatory
diseases such as atherosclerosis.
[Back to top]
Macrophage Migration Inhibitory Factor: A Therapeutic
Target Across Inflammatory Diseases
Alberta Y. Hoi, Magdy N. Iskander and Eric F. Morand
Macrophage migration inhibitory factor (MIF), a cytokine originally
reported in the 1960s as the prototypic T lymphokine, has
emerged in recent years as a key factor regulating inflammatory
responses. Both by directly activating immune cells, and by
participating in activation entrained by other stimuli, MIF
is important in innate and adaptive immune responses as well
as tissue-specific mechanisms of damage. As a consequence
of its involvement in multiple stages of the immune-inflammatory
response, MIF has the potential to be involved in the pathogenesis
of a range of immune-mediated inflammatory diseases affecting
multiple organ systems. Diseases in which a role for MIF has
been strongly validated include rheumatoid arthritis, inflammatory
bowel disease, multiple sclerosis, atherosclerosis, asthma,
inflammatory liver disease, and most recently systemic lupus
erythematosus. Recent data have provided mechanisms of action
for MIF which further support its suitability as a therapeutic
target. Finally, MIF has a unique relationship with glucocorti-coids,
acting to counter-regulate their anti-inflammatory effects,
such that MIF antagonist therapy may be a direct route to
'steroid-sparing'.
Methods of targeting MIF therapeutically have also emerged
in recent years, based on the unique protein structure of
MIF which affords opportunities for direct antagonism by small
molecules, as well as by protein therapeutics such as mono-clonal
antibodies. Clinical trials of MIF antagonist therapies are
likely before the end of the current decade.
|
