20 research outputs found
Regulation of allergen-specific immune responses by CD4+ CD45R+ cells in patients with allergic contact dermatitis
Interleukin 33 and interleukin 4 regulate interleukin 31 gene expression and secretion from human laboratory of allergic diseases 2 mast cells stimulated by substance P and/or immunoglobulin E
Background: Cytokine interleukin (IL) 31 has emerged as an important
component of allergic and inflammatory diseases associated with
pruritus, such as atopic dermatitis (AD) and mastocytosis. Mast cells
(MC) are stimulated by allergic and nonallergic triggers, and play a
critical role in such diseases by secreting histamine and tryptase as
well as cytokines and chemokines. IL-33 has been reported to augment MC
responses, but its effect on secretion of IL-31 is not known.
Objectives: To investigate whether IL-33 can stimulate the secretion of
IL-31 from cultured human MCs and whether this response is augmented by
either the neuropeptide substance P (SP) or immunoglobulin E (IgE) and
anti-IgE in the absence or presence of IL-4.
Methods: Laboratory of Allergic Diseases (LAD2) human MCs were cultured
in StemProH-34 SFM medium supplemented by stem cell factor and were
stimulated either with IL-33 (10 ng /mL) or SP (2 mu M), or preincubated
with IgE (1 mu g/mL) overnight, and then stimulated with anti-IgE (1 mu
g/mL) for 24 hours. IL-31 gene expression was measured by quantitative
polymerase chain reaction, and protein was measured by enzyme-linked
immunosorbent assay.
Results: IL-33 (10 ng/mL) induces IL-31 gene expression, synthesis, and
secretion from LAD2 cells in the absence of degranulation, whereas SP
and IgE on their own have no effect. However, the effect of IL-33 is
augmented by SP (2 mu M) and/or IgE and anti-IgE (1 mu g/mL both) and
especially their combination. Moreover, this response is significantly
further increased when LAD2 cells are cultured in the presence of IL-4.
Conclusion: These findings provide evidence that IL-33 induced secretion
of IL-31 from LAD2 MC, an action augmented by novel neuroimmune
interactions that may help in the development of new treatments of
allergic and inflammatory diseases, especially AD and mastocytosis
Interleukin 33 and interleukin 4 regulate interleukin 31 gene expression and secretion from human laboratory of allergic diseases 2 mast cells stimulated by substance P and/or immunoglobulin E
The Effect of Atopy in the Prevalence of Contact Sensitization: The Experience of a Greek Referral Center
Contact dermatitis is a well-known skin condition, which is related to stimuli and environmental exposure to chemicals, affecting all ages as well as both genders. In the present work, we attempt to investigate the patterns of contact sensitization, with respect to the personal history of atopy (AT), in Greece in a large number of allergens, using patch testing. The retrospective analysis included clinical routine data of 1978 patients collected from 2014 to 2016 in the Laboratory of Patch Testing, National Referral Centre of Occupational Dermatoses. Sensitization, in all cases, was tested with 28 allergens of the European baseline series as adjusted to our local circumstances and clinical experience. A total population of 1978 patients was evaluated, with a male-to-female ratio of 0.45 (1359 females/619 males). From our patient cohort, 693 (35%) patients were evaluated with a history of atopy, while 1285 (65%) were nonatopic. The five most prevalent allergens in the total population without AT were nickel sulphate 5% (15.47%), fragrance mix (I) 8% (9.10%), balsam of Peru (6.47%), cobalt chloride 1% (4.70%), and thiomersal 0.1% (4.10%). Respectively, in the total population with AT, the five most prevalent allergens were nickel sulphate 5% (10.36%), fragrance mix (I) 8% (5.11%), balsam of Peru (3.29%), thiomersal 0.1% (3.03%), and cobalt chloride 1% (2.78%). Contact dermatitis surveillance is of great importance towards the clinical and systematic understanding of the disease. Further studies should be directed towards that end, in order to facilitate more effective health policies
Quercetin Is More Effective than Cromolyn in Blocking Human Mast Cell Cytokine Release and Inhibits Contact Dermatitis and Photosensitivity in Humans
Mast cells are immune cells critical in the pathogenesis of allergic,
but also inflammatory and autoimmune diseases through release of many
pro-inflammatory cytokines such as IL-8 and TNF. Contact dermatitis and
photosensitivity are skin conditions that involve non-immune triggers
such as substance P (SP), and do not respond to conventional treatment.
Inhibition of mast cell cytokine release could be effective therapy for
such diseases. Unfortunately, disodium cromoglycate (cromolyn), the only
compound marketed as a mast cell “stabilizer”, is not particularly
effective in blocking human mast cells. Instead, flavonoids are potent
anti-oxidant and anti-inflammatory compounds with mast cell inhibitory
actions. Here, we first compared the flavonoid quercetin (Que) and
cromolyn on cultured human mast cells. Que and cromolyn (100 mu M) can
effectively inhibit secretion of histamine and PGD(2). Que and cromolyn
also inhibit histamine, leukotrienes and PGD(2) from primary human cord
blood-derived cultured mast cells (hCBMCs) stimulated by IgE/Anti-IgE.
However, Que is more effective than cromolyn in inhibiting IL-8 and TNF
release from LAD2 mast cells stimulated by SP. Moreover, Que reduces
IL-6 release from hCBMCs in a dose-dependent manner. Que inhibits
cytosolic calcium level increase and NF-kappa B activation.
Interestingly, Que is effective prophylactically, while cromolyn must be
added together with the trigger or it rapidly loses its effect. In two
pilot, open-label, clinical trials, Que significantly decreased contact
dermatitis and photosensitivity, skin conditions that do not respond to
conventional treatment. In summary, Que is a promising candidate as an
effective mast cell inhibitor for allergic and inflammatory diseases,
especially in formulations that permit more sufficient oral absorption
INCREASED AFFECTED SKIN GENE EXPRESSION AND SERUM LEVELS OF THYMIC STROMAL LYMPHOPOIETIN IN ATOPIC DERMATITIS
Mitochondrial dysfunction in affected skin and increased mitochondrial DNA in serum from patients with psoriasis
Psoriasis is characterized by keratinocyte proliferation and chronic
inflammation, but the pathogenesis is still unclear. Dysregulated
mitochondria (mt) could lead to reduced apoptosis and extracellular
secretion of mtDNA, acting as “innate pathogen” triggering
inflammation. Serum was obtained from healthy volunteers and psoriatic
patients. Mitochondrial DNA was extracted from the serum and amplified
with quantitative PCR (qPCR). Punch biopsies were obtained from lesional
and non-lesional psoriatic skin (10 cm apart) and from healthy
volunteers, were placed in RNA later and were stored at -80 degrees C
until RNA was extracted and cDNA was synthesized; gene expression of
uncoupling protein 2 (UCP2), Dynamin-related protein 1 (Drp1) and
calcineurin, involved in the regulation of mitochondria function, was
detected with qPCR. Mitochondrial DNA was significantly increased (7s, P
= 0.0496 and Cytochrome B, CytB, P = 0.0403) in the serum of psoriatic
patients (n = 63) as compared to controls (n = 27). Gene expression was
significantly reduced for UCP2 (P = 0.0218), Drp1 (P = 0.0001) and
calcineurin (P = 0.0001) in lesional psoriatic skin, as compared to
non-lesional or control skin. Increased serum extracellular mtDNA in
psoriatic patients and decreased expression of mitochondrial regulatory
proteins in psoriatic skin suggest increased inflammation and reduced
keratinocyte apoptosis, respectively. Inhibitors of mtDNA secretion
and/or UCP2 stimulants may be potential treatment options
Quercetin Is More Effective than Cromolyn in Blocking Human Mast Cell Cytokine Release and Inhibits Contact Dermatitis and Photosensitivity in Humans
<div><p>Mast cells are immune cells critical in the pathogenesis of allergic, but also inflammatory and autoimmune diseases through release of many pro-inflammatory cytokines such as IL-8 and TNF. Contact dermatitis and photosensitivity are skin conditions that involve non-immune triggers such as substance P (SP), and do not respond to conventional treatment. Inhibition of mast cell cytokine release could be effective therapy for such diseases. Unfortunately, disodium cromoglycate (cromolyn), the only compound marketed as a mast cell “stabilizer”, is not particularly effective in blocking human mast cells. Instead, flavonoids are potent anti-oxidant and anti-inflammatory compounds with mast cell inhibitory actions. Here, we first compared the flavonoid quercetin (Que) and cromolyn on cultured human mast cells. Que and cromolyn (100 µM) can effectively inhibit secretion of histamine and PGD<sub>2</sub>. Que and cromolyn also inhibit histamine, leukotrienes and PGD<sub>2</sub> from primary human cord blood-derived cultured mast cells (hCBMCs) stimulated by IgE/Anti-IgE. However, Que is more effective than cromolyn in inhibiting IL-8 and TNF release from LAD2 mast cells stimulated by SP. Moreover, Que reduces IL-6 release from hCBMCs in a dose-dependent manner. Que inhibits cytosolic calcium level increase and NF-kappa B activation. Interestingly, Que is effective prophylactically, while cromolyn must be added <u>together</u> with the trigger or it rapidly loses its effect. In two pilot, open-label, clinical trials, Que significantly decreased contact dermatitis and photosensitivity, skin conditions that do not respond to conventional treatment. In summary, Que is a promising candidate as an effective mast cell inhibitor for allergic and inflammatory diseases, especially in formulations that permit more sufficient oral absorption.</p> </div
Human mast cell degranulation and preformed TNF secretion require mitochondrial translocation to exocytosis sites: Relevance to atopic dermatitis
Background: Mast cells derive from hematopoietic cell precursors and
participate in tissue allergic, immune, and inflammatory processes. They
secrete many mediators, including preformed TNF, in response to
allergic, neuropeptide, and environmental triggers. However, regulation
of mast cell degranulation is not well understood.
Objective: We investigated the role of mitochondrial dynamics in
degranulation of human cultured mast cells.
Methods: Human umbilical cord blood-derived mast cells (hCBMCs) and
Laboratory of Allergic Diseases 2 (LAD2) mast cells were examined by
confocal and differential interference contrast microscopy during
activation by IgE/antigen and substance P (SP). Mast cells in control
and atopic dermatitis (AD) skin were evaluated by transmission electron
microscopy. LAD2 cells were pretreated with mitochondrial division
inhibitor, a dynamin-related protein 1 (Drp1) inhibitor, and small
interfering RNA for Drp1, which is necessary for mitochondrial fission
and translocation. Calcineurin and Drp1 gene expression was analyzed in
stimulated LAD2 cells and AD skin biopsies.
Results: Stimulation of hCBMCs with IgE/antigen or LAD2 cells with SP
leads to rapid (30 minutes) secretion of preformed TNF. Degranulation is
accompanied by mitochondrial translocation from a perinuclear location
to exocytosis sites. Extracellular calcium depletion prevents these
effects, indicating calcium requirement. The calcium-dependent
calcineurin and Drp1 are activated 30 minutes after SP stimulation.
Reduction of Drp1 activity by mitochondrial division inhibitor and
decrease of Drp1 expression using small interfering RNA inhibit
mitochondrial translocation, degranulation, and TNF secretion.
Mitochondrial translocation is also evident by transmission electron
microscopy in skin mast cells from AD biopsies, in which gene expression
of calcineurin, Drp1, and SP is higher than in normal skin.
Conclusion: Human mast cell degranulation requires mitochondrial
dynamics, also implicated in AD. (J Allergy Clin Immunol
2011;127:1522-31.