An Adjuvant-Free Mouse Model of Transdermal Sensitization and Oral Elicitation of Anaphylaxis to Shellfish.

Background: Shellfish (SF) allergy is a leading cause of systemic anaphylaxis in humans. An adjuvant-free mouse model to evaluate allergenicity and oral anaphylaxis to SF is currently unavailable. Here, we tested the hypothesis that transdermal exposure (TDE) to SF protein extract (SFPE) not only elicits a systemic allergic immune response but also will clinically sensitize mice for oral anaphylaxis.

Cardiac mMCP-4+ mast cell expansion and elevation of IL-6, and CCR1/3 and CXCR2 signaling chemokines in an adjuvant-free mouse model of tree nut allergy.

Background: Nut allergy is a growing and potentially fatal public health problem. We have previously reported a novel mouse model of near-fatal hazelnut (HN) allergy that involves transdermal sensitization followed by oral elicitation of allergic reactions. Here we studied the cardiac mast cell and cardiac tissue responses during oral nut induced allergic reaction in this mouse model.

Role of myeloid-specific G-protein coupled receptor kinase-2 in sepsis.

Previous studies have implicated a critical role for G-protein coupled receptor kinase-2 (GRK2) in sepsis owing to its ability to regulate inflammatory response and chemotaxis of immune cells. We therefore, hypothesized that deletion of GRK2 in myeloid cells would significantly modulate the pathogenesis of polymicrobial sepsis. To test this hypothesis, we induced cecal ligation and puncture (CLP), in mice with myeloid-specific deletion of GRK2 and the corresponding GRK2 wild type littermates and determined the inflammatory response (IL-6 and IL-10), immune cell infiltration, bacterial load and survival.

Overlapping and distinct roles of GRK5 in TLR2-, and TLR3-induced inflammatory response in vivo.

G-protein coupled receptor kinase-5 (GRK5) is a recently described NFκB regulator in TLR4 signaling pathway. To determine whether the role of GRK5 is MyD88- or TRIF-dependent, we injected wild type and GRK5 knockout mice with Pam3CSK4 (MyD88-dependent TLR1/2 ligand) and Poly(I:C) (TRIF-dependent TLR3 ligand) and examined the in vivo systemic inflammatory response. Our results demonstrate that GRK5 regulates IL-12p40 and G-CSF via a mechanism that is common to both MyD88 and TRIF.

Myeloid-specific GPCR kinase-2 negatively regulates NF-κB1p105-ERK pathway and limits endotoxemic shock in mice.

G-protein-coupled receptor kinase 2 (GRK2) is a member of a kinase family originally discovered for its role in the phosphorylation and desensitization of G-protein-coupled receptors. It is expressed in high levels in myeloid cells and its levels are altered in many inflammatory disorders including sepsis. To address the physiological role of myeloid cell-specific GRK2 in inflammation, we generated mice bearing GRK2 deletion in myeloid cells (GRK2▵mye).

Regulation of lipopolysaccharide-induced inflammatory response and endotoxemia by beta-arrestins.

Beta-arrestins are scaffolding proteins implicated as negative regulators of TLR4 signaling in macrophages and fibroblasts. Unexpectedly, we found that beta-arrestin-1 (beta-arr-1) and -2 knockout (KO) mice are protected from TLR4-mediated endotoxic shock and lethality. To identify the potential mechanisms involved, we examined the plasma levels of inflammatory cytokines/chemokines in the wild-type (WT) and beta-arr-1 and -2 KO mice after lipopolysaccharide (LPS, a TLR4 ligand) injection.

Long-term characteristics of hazelnut allergy in an adjuvant-free mouse model.

Background: Clinically it is recognized that tree nut allergies such as hazelnut allergy are not usually outgrown. Specific mechanisms underlying the persistence of such food allergies are incompletely understood. Here we studied the natural history and the long-term immune and clinical characteristics of hazelnut allergy in an adjuvant-free mouse model.

Development of an adjuvant-free cashew nut allergy mouse model.

Background: Cashew nut allergy is an emerging food allergy with a high risk of systemic anaphylaxis. Currently, an adjuvant-free animal model to study cashew nut allergy is not available.

Methods: BALB/c mice were exposed to cashew nut protein using a transdermal sensitization protocol that does not use adjuvant.

An adjuvant-free mouse model of tree nut allergy using hazelnut as a model tree nut.

Background: Tree nut allergy, a major group of food allergy, is often linked to fatal or near-fatal systemic anaphylaxis. Currently, an adjuvant-free mouse model to study tree nut hypersensitivity is unavailable. Here we tested the hypothesis that transdermal exposure to hazelnut, a model tree nut, without the use of an adjuvant is sufficient to sensitize mice for immediate hypersensitivity reaction to oral hazelnut challenge.

Optimization, comparison, and application of colorimetric vs. chemiluminescence based indirect sandwich ELISA for measurement of human IL-23.

Currently, there is neither a published ELISA method nor it is clear whether chemiluminescence substrates would provide better sensitivity vs. colorimetric substrates for measuring human IL-23-a recently described Type-1 immunity associated cytokine. Initially, we optimized a colorimetric ELISA using p-nitro-phenyl phosphate substrate.

Allergic and anaphylactic response to sesame seeds in mice: identification of Ses i 3 and basic subunit of 11s globulins as allergens.

Background: Allergy to sesame seeds is an emerging food allergy of a serious nature due to a high risk of systemic anaphylaxis. Although a mouse model to study sesame anaphylaxis is desirable, currently it is not available. Here, using a transdermal exposure model system, we tested the hypothesis that sesame seed elicits IL-4-associated IgE antibody response with consequent clinical sensitization in mice.