BACKGROUND: A small subgroup of atopic dermatitis (AD) patients show low total and allergen-specific immunoglobulin (IgE) levels. This subgroup has been termed 'intrinsic' AD (IAD) as compared to its counterpart 'extrinsic' AD (EAD). However, the difference of cytokine expression between IAD and EAD has not been fully understood. OBJECTIVE: To compare the expression of various inflammatory cytokines in the peripheral blood mononuclear cells (PBMCs) and lesional skin of patients with IAD and EAD, which are known to be associated with AD pathophysiology. METHODS: We assessed the protein levels of cytokines in the PBMCs and lesional skin. We evaluated the levels of IL-3, IL-4, IL-5, IL-6, IL-10, IL-13, FcepsilonRI and FcepsilonRII from the PBMCs and lesional skin of patients with IAD and EAD. RESULTS: The patients with EAD had elevated levels of the IL-3 expression in their PBMCs and elevated levels of FcepsilonRI in their lesional skin compared to that of the patients with IAD. The expression of other cytokines did not differ in the PBMCs and lesional skin from the two subgroups. CONCLUSION: This study suggests that IL-3 could be associated with the pathophysiology of EAD as compared to that of IAD, along with FcepsilonRI which was previously shown to be highly expressed in EAD patients.
Cytokines ; Dermatitis, Atopic ; Humans ; Immunoglobulins ; Interleukin-10 ; Interleukin-13 ; Interleukin-3 ; Interleukin-4 ; Interleukin-5 ; Interleukin-6 ; Skin

Cytokines play a pivotal role in maintaining bone homeostasis. Osteoclasts (OCs), the sole bone resorbing cells, are regulated by numerous cytokines. Macrophage colony-stimulating factor and receptor activator of NF-κB ligand play a central role in OC differentiation, which is also termed osteoclastogenesis. Osteoclastogenic cytokines, including tumor necrosis factor-α, IL-1, IL-6, IL-7, IL-8, IL-11, IL-15, IL-17, IL-23, and IL-34, promote OC differentiation, whereas anti-osteoclastogenic cytokines, including interferon (IFN)-α, IFN-β, IFN-γ, IL-3, IL-4, IL-10, IL-12, IL-27, and IL-33, downregulate OC differentiation. Therefore, dynamic regulation of osteoclastogenic and anti-osteoclastogenic cytokines is important in maintaining the balance between bone-resorbing OCs and bone-forming osteoblasts (OBs), which eventually affects bone integrity. This review outlines the osteoclastogenic and anti-osteoclastogenic properties of cytokines with regard to osteoimmunology, and summarizes our current understanding of the roles these cytokines play in osteoclastogenesis.
Cytokines ; Homeostasis ; Interferons ; Interleukin-1 ; Interleukin-10 ; Interleukin-11 ; Interleukin-12 ; Interleukin-15 ; Interleukin-17 ; Interleukin-23 ; Interleukin-27 ; Interleukin-3 ; Interleukin-33 ; Interleukin-4 ; Interleukin-6 ; Interleukin-7 ; Interleukin-8 ; Macrophage Colony-Stimulating Factor ; Necrosis ; Osteoblasts ; Osteoclasts ; RANK Ligand

How Th2 immunity develops in vivo remains obscure. Basophils have been considered key innate cells producing IL-4, a cytokine essential for Th2 immunity. Increasing evidence suggests that basophils are dispensable for the initiation of Th2 immunity. In this study, we revisited the role of basophils in Th2 immune responses induced by various types of adjuvants. Mice deficient in IL-3 or IL-3 receptor, in which basophil lymph node recruitment is completely abolished, fully developed wild type level Th2 CD4 T cell responses in response to parasite antigen or papain immunization. Similar finding was also observed in mice where basophils are inducibly ablated. Interestingly, IL-4-derived from non-T cells appeared to be critical for the generation of IL-4-producing CD4 T cells. Other Th2 promoting factors including IL-25 and thymic stromal lymphopoietin (TSLP) were dispensable. Therefore, our results suggest that IL-3- and basophil-independent in vivo Th2 immunity develops with the help of non-T cell-derived IL-4, offering an additional mechanism by which Th2 type immune responses arise in vivo.
Animals ; Basophils ; Immunization ; Interleukin-3 ; Interleukin-4* ; Lymph Nodes ; Mice ; Papain ; Parasites ; Receptors, Interleukin-3 ; T-Lymphocytes

Several pathophysiologic features of allergic inflammation, such as T(H) differentiation, the regulation of IgE, eosinophilia, mast cell proliferation, and cellular recruitment, are regulated by various cytokines. It has been of particular interest to investigate the underlying mechanism in the preferential activation of T(H2) cells by allergens. Although interleukin (IL)-4 is the major determinant of T(H2) differentiation, the original cellular source of IL-4 and the nature of the interaction between IL-4 and TH2 differentiation remain unclear. Recent studies have demonstrated that the regulation of IgE depends primarily on the functional activities of IL-4, IL-13, and IFN-gamma. Eosinophilia and an increased number of mast cells characterize allergic inflammation, which is a T cell-dependent process. IL-5 is the major chemotactic and activating factor of eosinophils. Mast cell proliferation results from several cytokines, including IL-3, IL-9, and IL-10. It has been suggested that, in the late phase reaction of allergic inflammation, proinflammatory cytokines released from mast cells, eosinophils, and T(H2) cells enhance the expression of adhesion molecules and chemokines that further promote the allergic cellular milieu.
Allergens ; Chemokines ; Cytokines* ; Eosinophilia ; Eosinophils ; Hypersensitivity* ; Immunoglobulin E ; Inflammation ; Interleukin-10 ; Interleukin-13 ; Interleukin-3 ; Interleukin-4 ; Interleukin-5 ; Interleukin-9 ; Interleukins ; Mast Cells

Several pathophysiologic features of allergic inflammation, such as T(H) differentiation, the regulation of IgE, eosinophilia, mast cell proliferation, and cellular recruitment, are regulated by various cytokines. It has been of particular interest to investigate the underlying mechanism in the preferential activation of T(H2) cells by allergens. Although interleukin (IL)-4 is the major determinant of T(H2) differentiation, the original cellular source of IL-4 and the nature of the interaction between IL-4 and TH2 differentiation remain unclear. Recent studies have demonstrated that the regulation of IgE depends primarily on the functional activities of IL-4, IL-13, and IFN-gamma. Eosinophilia and an increased number of mast cells characterize allergic inflammation, which is a T cell-dependent process. IL-5 is the major chemotactic and activating factor of eosinophils. Mast cell proliferation results from several cytokines, including IL-3, IL-9, and IL-10. It has been suggested that, in the late phase reaction of allergic inflammation, proinflammatory cytokines released from mast cells, eosinophils, and T(H2) cells enhance the expression of adhesion molecules and chemokines that further promote the allergic cellular milieu.
Allergens ; Chemokines ; Cytokines* ; Eosinophilia ; Eosinophils ; Hypersensitivity* ; Immunoglobulin E ; Inflammation ; Interleukin-10 ; Interleukin-13 ; Interleukin-3 ; Interleukin-4 ; Interleukin-5 ; Interleukin-9 ; Interleukins ; Mast Cells

BACKGROUND: The megakaryopoiesis and platelet production is regulated by several hematopoietc factors such as thrombopoietin (TPO), interleukin-11 (IL-11) and interleukin-3 (IL-3). IL-11 is a potent stimulator of megakaryopoiesis in vivo, and acts primarily as a megakaryocyte maturation factor in vitro and it can act synergistically with IL-3 and TPO. We performed this study to investigate the effects of recombinant human IL-11 (rhIL-11) with other hematopoietic factors on megakaryocyte colony formation in vitro. METHODS: CD34+ cells were separated from umbilical cord blood and megakaryocyte colonies using MegaCult Assay Kit were cultured with rhIL-11, recombinant human IL-3 (rhIL-3), and recombinant human TPO (rhTPO) for 7 and 14 days. The number and percentage of CD34+ and CD41a+ cells were determined by flowcytometry. RESULTS: The number of CD41a+ cells were 0.54+/-0.05x10(4) (rhIL-11 100 ng/ml), 5.32+.-0.23x10(4) (rhIL-3 100 ng/ml), and 8.76+/-0.15x10(4) (rhTPO 50 ng/ml) of total expanded cells during the culture of the purified CD34+ cells in liquid phase for 7 days. The number of CD41a+ cells were increased to 7.47+/-0.69x10(4) (rhIL-3 rhIL-11), 11.92+/-0.19x10(4) (rhTPO rhIL-11) of total expanded cells, respectively, during the culture of the purified CD34+ cells in liquid phase for 7 days in the presence of rhIL-11 (100 ng/ml). When the purified CD34+ cells were cultured in semisolid media including various concentration of rhIL-11, the megakaryocyte colonies were not formed. When the purified CD34+ cells were cultured with rhIL-11 and rhTPO or with rhIL-11 and rhIL-3, the number of megakaryocyte colonies were increased compared with rhTPO or rhIL-3 alone. CONCLUSION: These results indicate that IL-11 exerts a potent proliferative activity to colony forming unit-megakaryocyte from human umbilical cord blood, and it acts with other hematopoietic factors synergistically
Blood Platelets ; Fetal Blood* ; Humans ; Interleukin-11* ; Interleukin-3 ; Megakaryocytes ; Thrombopoietin ; Umbilical Cord*

The aim of this study was to find new idea for clinical treatment of aplastic anemia. Immune-mediated aplastic anemia mice were developed, IL-3 in the supernatant with PHA stimulating splenic cells was detected by ELISA, semi-quantiting analysis of IL-3R was performed by point hybridization. The results showed that the IL-3 level in the supernatant with PHA stimulating splenic cells of immune-mediated aplastic anemia mice was higher than controls, difference between them was significant (P <0.001), while amount of IL-3 receptor by semi-quantiting analysis was lower than control significantly. In conclusion, the IL-3 receptor expression level is important for pathogenesis and treatment strategy of aplastic anemia.
Anemia, Aplastic ; immunology ; pathology ; Animals ; Bone Marrow ; pathology ; Interleukin-3 ; analysis ; Mice ; Mice, Inbred BALB C ; Mice, Inbred DBA ; RNA, Messenger ; analysis ; Receptors, Interleukin-3 ; analysis ; genetics

BACKGROUND: Even though allergic disease is an inflammatory disease, main inflammatory cells and cytokines involved in this process are different from those in other inflammatory diseases. New therapeutic targets on allergic inflammation include eosinophils, mast cells, T lymphocytes and their cytokines activating those cells, so new antagonists acting on them are under many investigations. We extracted four iso-flavonoids from Sophorica japonica such as Sophi, Orbol, Luten, and Genistein which has been known PTK antagonist. We documented the three iso-flavonoids, except Genistein, had an antagonism on IL-5 using in vitro IL -5-induced eosinophil activation model and also in allergic mouse model sensitized by OA (ovualbumin). One of our data from mouse model, which was those three compounds blocked early allergic response near completely, suggested they might have an antagonism on IL-3, the major cytokine activating mast cell and basophils which control early allergic response mainly. OBJECTIVE: From the above results, we tried to find antagonistic effects of the compounds on IL-3 using IL-3 - induced eosinophil activation model in vitro. METHODS: LTC4 by RIA and degree of degranulation by light and electron microscopic examination were used as the activation markers of eosinophils. RESULTS: Among the compounds, Sophi was the most potent antagonist on IL-3 which induced LTC4 release and even on degranulation, and Orbol and Luten also had antagonism on them, but Genistein, an antagonist of PTK didn't show any antagonistic effects. CONCLUSION: We conclude that those three iso-flavonoids were IL-3 antagonists, and its mechanism might not be through PTK signaling.
Animals ; Basophils ; Cytokines ; Eosinophils* ; Flavonoids* ; Genistein ; Inflammation ; Interleukin-3 ; Interleukin-5 ; Leukotriene C4 ; Mast Cells ; Mice ; T-Lymphocytes

BACKGROUND: allergic disease is an inflammatory disease, whose main inflammatory cells are eosinophils, mast cells, and T lymphocytes. From that point, new therapeutic targets on allergic inflammation focusing on them are under investigation. We extracted four isoflavonoids from sophorica japonica such as sophi, orobol, genistin and genistein which are known PTK antagonists. We documented that these iso-flavonoids except genistein had an antagonism on IL-5 and IL-3 in vitro eosinophil activation and also in allergic mouse model sensitized by OA(ovualbumin). Their common action is due to the common beta chains. GM-CSF also share common beta chains, through which it activates eosinophils. OBJECTIVES: From the above results, We observed the antagonistic effects of these compounds on GM-CSF using eosinophil activation in vitro. METHODS: LTC4 which was detected by RIA and ECP by UniCAP were activation markers. RESULTS: Among those compounds, sophi was the most potent antagonist on GM-CSF induced LTC4 release and even on degranulation and orobol and genistin also had antagonism on them but genistein an antagonist of PTK did not show any antagonistic effects. CONCLUSION: From these results, We concluded these three iso-flavonoids were GM-CSF antagonists and the mechanism might not be through PTK signaling.
Animals ; Eosinophils ; Genistein ; Granulocyte-Macrophage Colony-Stimulating Factor ; Inflammation ; Interleukin-3 ; Interleukin-5 ; Leukotriene C4 ; Mast Cells ; Mice ; T-Lymphocytes

PURPOSE: The purpose of this study is to induce the differentiation of mast cells from human umbilical cord blood. METHODS: Mononuclear cells and CD34+ cells were obtained from cord blood and were cultured in the presence of stem cell factor, IL-3 and IL-6 in liquid suspension culture for 8 weeks. Mast cell was confirmed by Wright-Giemsa staining, immuno-histochemistry for tryptase and flowcytometry. RESULTS: When mononuclear cells were cultured for 4 weeks, the percentage of CD34-, CD117+ cells increased up to 8% in the presence of SCF only and 6.6% in the presence of SCF and IL-6. After 8 weeks of culture of CD34+ cells, the percentage of CD34-, CD117+ cells was highest at an average of 14.8% when cultured with SCF only, although absolute number of CD34-, CD117+ cells was higher when cultured in the presence of SCF, IL-3 and IL-6. CONCLUSION: We developed human mast cells from umbilical cord blood. However, some other factors such as combination or concentration of cytokines should be considered to enhance the efficiency of mast cell culture. In addition, mature cultured mast cells should be evaluated by flowcytometry as well as a special staining including immunohistochemistry.
Cytokines ; Fetal Blood* ; Humans* ; Immunohistochemistry ; Interleukin-3 ; Interleukin-6 ; Mast Cells* ; Stem Cell Factor ; Tryptases ; Umbilical Cord*