IgE Secretion Research Articles

Therapeutic effects of rosmarinic acid on airway responses in a murine model of asthma

Rosmarinic acid (RA) is an active component of a traditional Chinese herbal medicine. Previously, we reported that RA exerted a strong anti-inflammatory effect in a mouse acute lung injury model. Therefore, we hypothesized that RA might also have potential therapeutic effects in a murine model of asthma. In this study, we aimed to evaluate the anti-asthmatic activity of RA and explored its possible molecular mechanisms of action. Female BALB/c mice that had been sensitized to and challenged with ovalbumin (Ova) were treated with RA (20mg/kg) 1h after challenge. The results showed that RA greatly diminished the number of inflammatory cells and the production of Th2 cytokines in the bronchoalveolar lavage fluid (BALF); significantly reduced the secretion of total IgE, Ova-specific IgE, and eotaxin; and markedly ameliorated airway hyperresponsiveness (AHR) compared with Ova-induced mice. Histological studies further revealed that RA substantially decreased inflammatory cells infiltration and mucus hypersecretion compared with Ova-induced mice. Moreover, our results suggested that the protective effects of RA were mediated by the inhibition of JNK and p38 MAPK phosphorylation and nuclear factor-κB (NF-κB) activation. Furthermore, RA treatment resulted in a significant reduction in the mRNA expression of AMCase, CCL11, CCR3, Ym2 and E-selectin in lung tissue. These findings suggest that RA may effectively delay the development of airway inflammation and could thus be used as a therapy for allergic asthma.

Antigen-presenting cell-derived IL-6 restricts the expression of GATA3 and IL-4 by follicular helper T cells.

Follicular helper T cells (Tfh) support high-affinity Ab production by germinal center B cells through both membrane interactions and secretion of IL-4 and -21, two major cytokines implicated in B-cell survival and Ab class switch. Tfh-2 cells recently emerged in humans as a strong IL-4 producer Tfh cell subset implicated in both autoimmune and allergic diseases. Although the molecular mechanisms governing Tfh cell differentiation from naive T cells have been widely described, much less is known about the regulation of cytokine secretion by mouse Tfh-2 cells. The purpose of our study was to evaluate the role of dendritic cell-derived IL-6 in fine-tuning cytokine secretion by Tfh cells. Our results demonstrate that priming of Th cells by IL-6-deficient antigen-presenting dendritic cells preferentially leads to accumulation of a subset of Tfh cells characterized by high expression of GATA3 and IL-4, associated with reduced production of IL-21. STAT3-deficient Tfh cells also overexpress GATA3, suggesting that early IL-6/STAT3 signaling during Tfh cell development inhibits the expression of a set of genes associated with the Th2 differentiation program. Overall, our data indicate that IL-6/STAT3 signaling restrains the expression of Th2-like genes in Tfh cells, thus contributing to the control of IgE secretion in vivo.

The anti-inflammatory SSEDIKE peptide from Amaranth seeds modulates IgE-mediated food allergy

The in vivo immunomodulatory effect of a bioactive peptide from Amaranthus hypochondriacus grains in an IgE-mediated food allergy mouse model was examined. The synthetic SSEDIKE peptide was orally administered to prevent food allergy. Upon oral challenge with milk allergens we observed an alleviation of hypersensitivity symptoms with negativization of skin test, a significant inhibition of specific IgE and IgG1 secretion, a substantial reduction in the secretion of IL-5 and IL-13 by antigen-stimulated spleen cells and mucosal reduction of transcripts coding for ccl20, gata-3 and nf-kb. In addition tgf-β and foxp3 mRNA levels were up-regulated in jejunum. The charged SSEDIKE peptide from Amaranth inhibited the allergy reaction in a mouse model of food allergy, with suppression of IgE secretion and control of the intestinal inflammation preventing the activation of NF-κB, which might be attributed to the induction of local tolerance.

Regulation of Exacerbated Immune Responses in Human Peripheral Blood Cells by Hydrolysed Egg White Proteins.

The anti-allergic potential of egg white protein hydrolysates (from ovalbumin, lysozyme and ovomucoid) was evaluated as their ability to hinder cytokine and IgE production by Th2-skewed human peripheral blood mononuclear cells (PBMCs), as well as the release of pro-inflammatory factors and generation of reactive oxygen species from Th1-stimulated peripheral blood leukocytes (PBLs). The binding to IgE of egg allergic patients was determined and the peptides present in the hydrolysates were identified. The hydrolysates with alcalase down-regulated the production of Th2-biased cytokines and the secretion of IgE to the culture media of Th2-skewed PBMCs, and they significantly neutralized oxidative stress in PBLs. The hydrolysates of ovalbumin and ovomucoid with pepsin helped to re-establish the Th1/Th2 balance in Th2-biased PBMCs, while they also inhibited the release of pro-inflammatory mediators and reduced oxidative stress in PBLs treated with inflammatory stimuli. The hydrolysates with alcalase, in addition to equilibrating Th2 differentiation, exhibited a low IgE-binding. Therefore, they would elicit mild allergic reactions while retaining T cell-stimulating abilities, which might correlate with an anti-allergic benefit.

Prostaglandins E2 signal mediated by receptor subtype EP2 promotes IgE production in vivo and contributes to asthma development

Prostaglandins E2 (PGE2) has been shown to enhance IgE production by B cells in vitro. The physiological and pathological relevance of this phenomenon and the underlying molecular mechanism, however, remain to be elucidated. B cells from wild type and EP2-deficient mice were compared in culture for their responses to PGE2 in terms of IgE class switching and production. Ovalbumin (OVA)-induced asthma models were used to evaluate the impact of EP2-deficiency on IgE responses and the development of asthma. PGE2 promoted IgE class switching, generation of IgE+ cells and secretion of IgE by B cells stimulated with LPS+IL4. These effects were much attenuated as a consequence of EP2 deficiency. Consistent with the in vitro data, EP2-deficient mice showed a markedly suppressed IgE antibody response and developed less pronounced airway inflammation in the OVA-induced asthma model. Mechanistic studies demonstrated that PGE2, in an EP2-depedent manner, enhanced STAT6 activation induced by IL-4, thereby promoting the expression of IgE germline and post switch transcripts and the transcription of activation-induced cytidine deaminase (AID). Collectively, these data support an important regulatory role of the PGE2-EP2-STAT6 signaling pathway in IgE response and allergic diseases.

Elm Tree (Ulmus parvifolia) Bark Bioprocessed with Mycelia of Shiitake (Lentinus edodes) Mushrooms in Liquid Culture: Composition and Mechanism of Protection against Allergic Asthma in Mice.

Mushrooms can break down complex plant materials into smaller, more digestible and bioactive compounds. The present study investigated the antiasthma effect of an Ulmus parvifolia bark extract bioprocessed in Lentinus edodes liquid mycelium culture (BPUBE) against allergic asthma in chicken egg ovalbumin (OVA)-sensitized/challenged mice. BPUBE suppressed total IgE release from U266B1 cells in a dose-dependent manner without cytotoxicity. Inhibitory activity of BPUBE against OVA-specific IgE secretion in bronchoalveolar lavage fluid (BALF) was observed in OVA-sensitized/challenged asthmatic mice. BPUBE also inhibited OVA-specific IgG and IgG1 secretion into serum from the allergic mice, suggesting the restoration of a Th2-biased immune reaction to a Th1/Th2-balanced status, as indicated by the Th1/Th2 as well as regulatory T cell (Treg) cytokine profile changes caused by BPUBE in serum or BALF. Inflammatory cell counts in BALF and lung histology showed that leukocytosis and eosinophilia induced by OVA-sensitization/challenge were inhibited by the oral administration of BPUBE. Amelioration of eosinophil infiltration near the trachea was associated with reduced eotaxin and vascular cell adhesion molecule-1 (VCAM-1) levels. Changes in proinflammatory mediator levels in BALF suggest that BPUBE decreased OVA-sensitization-induced elevation of leukotriene C4 (LTC4) and prostaglandin D2 (PGD2). The finding that asthma-associated biomarker levels of OVA-sensitized/challenged mice were much more inhibited with BPUBE treatment than NPUBE (not-bioprocessed Ulmus parvifolia extract) treatment suggested the production of new bioactive compounds by the mushroom mycelia that may be involved in enhancing the observed antiasthmatic properties. The possible relation of the composition determined by proximate analysis and GC/MS to observed bioactivity is discussed. The results suggest that the elm tree (Ulmus parvifolia) bark bioprocessed with mycelia of shiitake (Lentinus edodes) mushrooms has the potential to prevent and/or treat allergic asthma.

The C-C chemokine receptor 6 (CCR6) is crucial for Th2-driven allergic conjunctivitis

Allergic conjunctivitis from an allergen-driven Th2 response is characterized by conjunctival eosinophilic infiltration. Although CCL20–CCR6 axis has been reported to play a proinflammatory role in several murine models of autoimmune diseases including allergic diseases, their underlying mechanism needs to be investigated. We here examined whether CCL20–CCR6 axis could play a role in the development of allergic conjunctival inflammation using murine experimental allergic conjunctivitis (EAC) model induced by ovalbumin (OVA) allergen. Mice were challenged with consecutive 10days of OVA via conjunctival sac after systemic challenge with OVA and cholera toxin in alum. Several indicators for allergy were comparatively evaluated in wild-type and CCR6 KO EAC mice. Wild-type mice challenged with OVA via conjunctival sac following systemic challenge with OVA in alum had severe allergic conjunctivitis. The absence of CCR6 suppressed IgE secretion and allergic conjunctival inflammation. Reduced allergic inflammation was ascribable to reduced cytokine responses from Th-2 type in draining lymph node although Th17, regulatory T cells and dendritic cell subsets are not affected by the absence of CCR6. In addition, neutralization of CCR6 ligand, CCL20 could repress allergic conjunctival inflammation. Our findings suggested that CCR6 might be crucial for optimal development of Th2 immune responses and further allergic conjunctival inflammation in EAC model.

Impaired Function of CD5+CD19+CD1dhi B10 Cells on IgE Secretion in an Atopic Dermatitis-Like Mouse Model.

Atopic dermatitis (AD) is a chronic inflammatory pruritic skin disease in which the pathogenic mechanism is complicated and not completely understood. Reports on the role of regulated cells in AD have recently evolved to regulate B cells, which may play a role in allergic inflammation as well. In the present study, we examined the frequency and regulatory function of CD5+CD19+CD1dhi B10 cells in an AD-like mouse model. Our results showed that the percentage of CD5+CD19+CD1dhi B10 cells increased while the frequency of IL-10-producing B cells in CD19+B cells decreased in the mice of AD group. Moreover, no difference in the percentage of B10pro+B10 cells was observed between the AD and control groups. Strikingly, B10 cells from control mice effectively inhibited IgE secretion, whereas the suppressive function of B10 cells from the AD mice was significantly decreased, which was similar to that observed in the group without B10. Altogether, these results suggest that the number of IL-10-producing B cells decreased in the AD group and these cells showed a defective regulatory function on IgE secretion.

The effect of mesenchymal stem cells on leukocyte allergen-specific reactions in the case of atopic hypersensitivity

Buffy coat samples containing lymphocytes, monocytes, and granulocytes were obtained from the peripheral blood of 16 donors who had clinical manifestations of atopic hypersensitivity in their medical background. After ex vivo incubation with donor-specific allergens, the percentage of Band T-lymphocytes and natural killers remained unchanged. Incubation of buffy coat cells with allergens induced the production of IgE and IL-4 in all assayed samples. In 13 out of 16 cases, the reaction to contact with an allergen was also evident in the increasing of T-activated lymphocytes (CD3+, HLA-DR+) subpopulation. Cocultivation with mesenchymal stromal cells (MSCs) from bone marrow, adipose tissue and umbilical cord resulted in blocking of allergen-induced IgE and IL-4 secretion and increase in the subpopulation of HLA-DR+ T-lymphocytes. There was no significant difference in the effect of MSCs isolated from three different sources on allergenspecific responses of leukocytes. Coculturing of leukocytes with MSCs from all three sources increased the content of regulatory T-lymphocytes by approximately 30%. Thus, the immunomodulatory activity of MSCs in vitro results in blocking of the effector phase of allergic reactions.

Docosahexaenoic Acid Alleviates Atopic Dermatitis in Mice by Generating T Regulatory Cells and M2 Macrophages

Han et al. (this issue) describe a novel mechanism by which docosahexaenoic acid (DHA) may suppress atopic dermatitis symptoms in mice. They find that DHA induces FoxP3 T regulatory cells in vivo, M2 macrophages drive transforming growth factor-β and IL-10 conversion of CD4 T cells to CD4 FoxP3 T regulatory cells in vitro, and DHA-treated M2 macrophages suppress atopic dermatitis in mice.

Interleukin-21 suppresses the differentiation and functions of T helper 2 cells.

T helper type 2 (Th2) cells, which produce interleukin-4 (IL-4), IL-5 and IL-13, control immunity to all forms of allergic inflammatory responses. Interleukin-21 (IL-21) reduces allergic symptoms in murine models and inhibits IL-4-induced IgE secretion by B cells. However, whether or not IL-21 directly affects Th2 cells, which leads to reduced allergic symptoms, is unclear. In this study, we investigated the effects of IL-21 on the differentiation and effector functions of Th2 cells. We found that IL-21 reduced the number of differentiated Th2 cells and these Th2 cells showed a diminished Th2 cytokine production. Interleukin-21 suppressed Th2 cytokine production of already polarized Th2 cells by down-regulation of transcription factor GATA-3. It also induced apoptosis of Th2 cells with decreased anti-apoptotic factor Bcl-2. Intranasal administration of IL-21 at the beginning of ovalbumin (OVA) sensitization or before OVA challenge decreased Th2 cytokines in the bronchoalveolar lavage fluid of OVA/alum-immunized allergic mice. In addition, the inhibitory effects of IL-21 on Th2 effector functions can also be found in allergic patients. Our results demonstrate that IL-21 suppresses the development of Th2 cells and functions of polarized Th2 cells. Hence, the administration of IL-21 may be considered for use as a preventive and therapeutic approach when dealing with Th2-mediated allergic diseases.

참치심장 에탄올 추출물의 항아토피 효과

Atopic dermatitis (AD) is a form of allergic skin inflammatory characterized by late eczematous skin lesions. The incidence of AD is increasing, and it causes problems with administrative costs. Therefore, development of an AD treatment with no side effects is needed. The purpose of this study was to evaluate tuna heart ethanol extract (THEE), a functional extract from by-product of tuna. AD was induced by spreading 2,4-dinitrochlorobenzene (DNCB) on the backside of BALB/c mice. The effect of THEE was tested by measuring skin clinical severity score, secretion of cytokines and IgE, and proliferation. Secretion of TNF-α, IL-4, IL-5, IL-13, and IgE significantly decreased in a THEE-independent manner. In contrast, levels of IL-10 and IFN-γ significantly increased in mice sera and splenocytes. In addition, THEE alleviated AD symptoms compared to the DNCB only group. In conclusion, these results demonstrate that THEE has an inhibitory effect on AD and may be a useful substance for the development of cosmeceuticals.

Saponins, Especially Platyconic Acid A, from Platycodon grandiflorum Reduce Airway Inflammation in Ovalbumin-Induced Mice and PMA-Exposed A549 Cells

We investigated the inhibitory effects of Platycodon grandiflorum root-derived saponins (Changkil saponins: CKS) on ovalbumin-induced airway inflammation in mice. CKS suppressed leukocytes number, IgE, Th1/Th2 cytokines, and MCP-1 chemokine secretion in bronchoalveolar lavage fluid. Also, ovalbumin-increased MUC5AC, MMP-2/9, and TIMP-1/-2 mRNA expression, NF-κB activation, leukocytes recruitment, and mucus secretion were inhibited by CKS treatment. Moreover, the active component of CKS, platyconic acid A (PA), suppressed PMA-induced MUC5AC mRNA expression (from 2.1 ± 0.2 to 1.1 ± 0.1) by inhibiting NF-κB activation (from 2.3 ± 0.2 to 1.2 ± 0.1) via Akt (from 3.7 ± 0.3 to 2.1 ± 0.2) (p < 0.01) in A549 cells. Therefore, we demonstrate that CKS or PA suppressed the development of respiratory inflammation, hyperresponsiveness, and remodeling by reducing allergic responses, and they may be potential herbal drugs for allergen-induced respiratory disease prevention.

Di-(2-ethylhexyl) phthalate adjuvantly induces imbalanced humoral immunity in ovalbumin-sensitized BALB/c mice ascribing to T follicular helper cells hyperfunction.

Di-(2-ethylhexyl) phthalate (DEHP) has been considered as a widespread environmental persistent organic pollutant and its potential concern on human health is raised by previous studies. In particular, children are more likely to be exposed to DEHP through gastrointestinal route and consequently are more susceptible to DEHP hazards. Some reports have uncovered a positive association between DEHP exposure and an increased prevalence of allergic diseases in infants and juveniles. Allergy is a hypersensitive reaction rooted in imbalanced humoral immunity. T follicular helper cell (Tfh), an important CD4(+) Th cell subset, until recently has been identified as a key player in humoral immune response by modifying B cells functions. Tfh cells are therefore perceived as the therapeutic target of immune disorders. In the present study, focusing on the newly confirmed Tfh cells, we examined the effects of DEHP on humoral immunity and investigated the underlying mechanisms. Using ovalbumin (OVA) sensitization weanling mice model under the condition of gastrointestinal exposure to DEHP, we found that DEHP acted as an immunoadjuvant to augment OVA-specific IgE and IgG1 production, amplified germinal center formation in lymphoid nodule, as well as stimulated the expansion of CD4(+)CXCR5(+)ICOS(+)/CD4(+)CXCR5(+)PD-1(+) Tfh cells and CD19(+)CD138(+)GL7(+) plasma cells. Based on the results of immune adoptive transfusion, DEHP-related anaphylactic response was ascribed to Tfh cells hyperfunction directly. We further proved that DEHP gavage together with OVA sensitization adjuvantly promoted the synthesis of cytokines IL-21 and IL-4 and the expression of transcription factors Bcl-6 and c-Maf in Tfh cells. In conclusion, our study demonstrates that DEHP has adjuvant toxic effects on Tfh cells by synthesizing an excess of cytokines IL-21 and IL-4 via over-expression of transcription factors Bcl-6 and c-Maf, leading to an increasing secretion of allergy-related IgE and IgG1.

Relation of intermediate-conductance Ca(2+)-activated K(+) channels with ability of proliferation, migration, invasion and IgE secretion of multiple myeloma cells

This study was aimed to investigate the effects of the intermediate-conductance Ca(2+)-activated K(+) (IKCa1) channels on the proliferation, migration, invasion ability and monoclonal immunoglobulin (IgE) secretion of multiple myeloma (MM) cells. Trypan blue exclusion was used to evaluate the impact of clotrimazole (CLO, an inhibitor of the KCa1) on the survival ability of MM cell line U266; transwell chamber and matrigel experiments were used to evaluate the impact of CLO on the ability of the migration and invasion of U266 cells; the influence of CLO on IgE secretion in U266 cells was detected by ELISA. The results showed that small dose of CLO ( ≤ 1.0 µmol/L) could not inhibit the viability of U266 cells. The Transwell and Matrigel invading tests displayed that the cell number moving into lower chamber of transwell decreased after U266 cells treated with small dose of CLO ( ≤ 1.0 µmol/L). After treating the cells with 1.00 µmol/L CLO for 24 h and 48 h, the concentration of IgE in cell supernatant was (4.98 ± 0.39) and (4.38 ± 0.32) ng/ml, while those in control group were (15.41 ± 1.88) and (19.73 ± 2.01) ng/ml, respectively, suggesting significant difference between them(P < 0.05). It is concluded that CLO can decrease the ability of migration and monoclonal immunoglobulin secretion of multiple myeloma cells by blocking the IKCa1, thus this study provides a new think for the targeted therapy of MM.

Adenovirus expressing IFN-λ1 (IL-29) attenuates allergic airway inflammation and airway hyperreactivity in experimental asthma.

Asthma is thought to result from the generation of T helper type 2 (Th2) responses, leading to bronchial inflammation. IFN-λ1 (also known as IL-29) is a recently described member of the IFN-λ family and has been shown to decrease production of Th2 cytokines in vitro. However, the role and mechanism of IFN-λ1 in asthma remain unknown. The aim of this study was to clarify the importance of IFN-λ1 in allergen-induced airway hyperresponsiveness (AHR) and inflammation. We used a murine model for ovalbumin (OVA)-induced asthma to examine the effect of intranasal delivery of recombinant adenovirus expressing human IFN-λ1 (Ad-hIFN-λ1) on AHR and allergic airway inflammation. Intranasal instillation of Ad-hIFN-λ1 before airway antigen challenge in OVA-immunized mice significantly decreased the severity of AHR and numbers of eosinophils and levels of IL-4, IL-5, and IL-13, but not IL-10 and IFN-γ; both in vivo, in the bronchoalveolar lavage fluid and in vitro, following stimulation of lymphocytes from spleens with OVA, compared with administration of a control virus (Ad-mock). Furthermore, Ad-hIFN-λ1 treatment inhibited serum IgE secretion and increased numbers of splenic CD4(+)CD25(+)FOXP3(+) Treg cells. Histological studies showed that Ad-hIFN-λ1 attenuated OVA-induced lung tissue eosinophilia. These results demonstrate that delivery of the Ad-hIFN-λ1 can mitigate allergic airway inflammation in experimental asthma. The potent immunoregulatory action of IFN-λ1 may offer a novel therapeutic approach to treat allergic asthma.

TRIF signaling is essential for TLR4-driven IgE class switching (IRM5P.707)

Abstract The TLR4 ligand LPS causes mouse B cells to undergo IgE and IgG1 isotype switching in the presence of IL-4. TLR4 activates two signaling pathways mediated by the adaptor molecules MyD88 and TRAM, which recruits TRIF. Following stimulation with LPS+IL-4, Tram-/- and Trif-/- B cells completely failed to express Cε germ line transcripts (GLT) and secrete IgE. In contrast, Myd88-/- B cells had normal expression of Cγ1 GLT, but reduced IgE secretion in response to LPS+IL-4. Following LPS+IL-4 stimulation, Cγ1 GLT expression was modestly reduced in Tram-/- and Trif-/- B cells, whereas Aicda expression and IgG1 secretion were reduced in Tram-/-,Trif-/-, and Myd88-/- B cells. B cells from all strains secreted normal amounts of IgE and IgG1 in response to anti-CD40+IL-4. Following stimulation with LPS+IL-4, Trif-/- B cells failed to sustain NFκB p65 nuclear translocation beyond 3 hours and had reduced binding of p65 to the Iε promoter. Addition of the NFκB inhibitor, JSH-23, to wild-type B cells 15 hours after LPS+IL-4 stimulation selectively blocked Cε GLT expression and IgE secretion, but had little effect on Cγ1 GLT expression and IgG secretion. These results indicate that sustained activation of NFκB driven by TRIF is essential for LPS+IL-4 driven activation of the Cε locus and class switching to IgE.

Specialized proresolving lipid mediators (SPMs) decrease human B cell IgE production: implications for allergy and asthma (HYP7P.309)

Abstract Resolution of inflammation is a biologically active process regulated by newly identified specialized proresolving lipid mediators (SPMs). These endogenous lipid-derived mediators promote the resolution of inflammation and maintain homeostasis by regulating the immune system. Little is known about the functions of SPMs on adaptive immune cells, such as B cells. Our laboratory has discovered that certain omega-3 fatty acid derived SPMs promote human B cell IgM and IgG antibody production in vitro. Human B cells also produce IgE antibodies, which play an essential role in the onset of inflammatory diseases, such as seasonal allergies and asthma. Here, we show that certain SPMs decrease human B cell IgE production in vitro. Omega-3-derived SPMs, 17-HDHA (17-hydoxydocosahexaenoic acid) and RvD1 (resolvin D1), strongly decreased the IgE production in B cells, as well as the number of IgE-secreting cells in peripheral blood of healthy and asthmatic human donors. In addition, 17-HDHA and RvD1 also reduced IgE production by the spontaneously IgE secreting multiple myeloma B cell line, U266. These results show that SPMs are non-immunosuppressive endogenous mediators that could specifically dampen IgE production and have potential as therapeutics for asthma. Moreover, SPMs might also be effective on other IgE-mediated inflammatory diseases such as atopic dermatitis.

Reduced C epsilon transcription by stabilization of CD23 in B cells (HYP7P.320)

Abstract The low affinity receptor for IgE (CD23, FcepsilonRII) is part of the broad regulatory network controlling IgE synthesis. It occurs as membrane and as soluble receptor generated in vivo by specific proteolysis. Targeting membrane CD23 with either IgE or anti-CD23 antibodies is believed to inhibit IgE synthesis. However, the mechanism behind this negative feedback remains unclear. This mechanism was investigated by examining the effect of anti-CD23 molecules in form of designed-ankyrin-repeat-proteins (DARPins) specific for CD23. Previous experiments using anti-CD23 antibodies were difficult to interpret as their Fc portion also mediate feedback mechanisms. The DARPins were produced as monovalent and bivalent molecules that were able to compete with the binding of IgE to CD23. The effects of anti-CD23 DARPins were assessed in an in vitro system using anti-CD40/IL-4 stimulated B cells. Treatment of B cells with anti-CD23 DARPins resulted in stabilization of membrane CD23. The released amount of soluble CD23 was reduced while CD23 mRNA expression was unchanged suggesting that the anti-CD23 DARPins stabilize CD23 and prevent its proteolysis. IgE secretion was significantly reduced by anti-CD23 DARPins. In addition, analysis of the epsilon transcript confirmed the reduction of IgE synthesis whereas IgG secretion was not influenced by the anti-CD23 DARPins. Further experiments will be performed to assess signalling pathways triggered by CD23 cross-linking.

Anti-atopic Activity of Sargassum micracanthum Ethanol Extracts

Da-Hyun Jeong , Koth-Bong-Woo-Ri Kim , Min-Ji Kim , Bo-Kyeong Kang , Si-Woo Bark , Won-Min Pak , Bo-Ram Kim , Hong-Min Park , Moo-Hyeog Im and Dong-Hyun Ahn . Microbiol. Biotechnol. Lett. 2014;42:82-8. https://doi.org/10.4014/kjmb.1401.01002