endothelin-1 and Dermatitis--Atopic

Topics: Animals; Animals, Genetically Modified; Calcium Signaling; Dermatitis, Atopic; Disease Models, Animal; Endothelin-1; Epidermis; Ganglia, Spinal; Keratinocytes; Nerve Growth Factor; Pruritus; Pyroglyphidae; Receptor, PAR-2

The role of soluble N-ethylmaleimide-sensitive factor attachment protein receptors in atopic dermatitis (AD) is unknown. This study identifies the function of soluble N-ethylmaleimide sensitive factor attachment protein receptor in AD-related cytokine secretion and epidermis-nerve communication. Herein, we report that various cytokines were simultaneously upregulated and coreleased in innate immunity-activated primary human keratinocytes. AD-related cytokines thymic stromal lymphopoietin, endothelin-1, and inflammatory tumor necrosis factor-α activated distinct but overlapping sensory neurons. Tumor necrosis factor-α potentiated thymic stromal lymphopoietin-induced Ca

Topics: Animals; Cells, Cultured; Cytokines; Dermatitis, Atopic; Disease Models, Animal; Endothelin-1; Epidermis; Ethylmaleimide; Gene Knockdown Techniques; Humans; Immunity, Innate; Keratinocytes; Mice; Mice, Inbred C57BL; Organ Culture Techniques; Sensory Receptor Cells; SNARE Proteins; Vesicle-Associated Membrane Protein 3

Endothelin-1 (ET-1) is associated with skin diseases such as atopic dermatitis (AD) and psoriasis. ET-1 is enhanced in the skin of patients AD and psoriasis. In addition, plasma levels of ET-1 are elevated in AD and psoriasis. Although both AD and psoriasis are T-cell-mediated skin diseases, the association between ET-1 and the T-cell immune response has not been clarified. To evaluate the role of ET-1 in inflammatory skin disease, we sought to investigate the effects of ET-1 on the functions of dendritic cells (DCs) and subsequent immune responses. For this purpose, we immunohistochemically confirmed the upregulation of ET-1 in the epidermis of patients with AD or psoriasis. ET-1 directly induced phenotypic maturation of bone marrow-derived DCs (BMDCs). In addition, ET-1 augmented the production of several cytokines and allogeneic stimulatory capacity of BMDCs. Interestingly, ET-1-activated BMDCs primed T cells to produce Th1 and Th17 cytokines, but not Th2 cytokines. These findings indicate that ET-1 polarizes the DC-T-cell response toward Th17/1 differentiation and may augment the persistent course of inflammatory skin diseases.

Topics: Animals; Cell Differentiation; Dendritic Cells; Dermatitis, Atopic; Endothelin-1; Enzyme-Linked Immunosorbent Assay; Epidermis; Flow Cytometry; Humans; Immunohistochemistry; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Psoriasis; Th1 Cells; Th17 Cells

Endothelin-1 (ET-1) has been reported to evoke histamine-independent pruritus in mammals. However, its association with pruritus or inflammation of atopic dermatitis (AD) has not been clarified. We sought to investigate the role of ET-1 in the skin inflammation of AD.. To examine the role of ET-1 in AD, we investigated the expression of ET-1 and IL-25 in the skin of an AD mouse model and patients with AD and examined the mutual regulatory relationship between ET-1 and IL-25, one of the important cytokines in AD, using the human HaCaT keratinocyte cell line.. We immunohistochemically confirmed the upregulation of ET-1 and IL-25 expression in the epidermis of both the AD mouse model and patients with AD. In vitro, IL-25 upregulated ET-1 mRNA and protein expression in a concentration- and time-dependent fashion in HaCaT cells. This IL-25-induced ET-1 expression was inhibited by ERK1/2 or JNK inhibitor. In a reciprocal manner, ET-1 also induced IL-25 upregulation. The enhancing effect of ET-1 on IL-25 was inhibited by an endothelin A receptor antagonist, ERK1/2 inhibitor, or p38 inhibitor, but not by an endothelin B receptor antagonist or JNK inhibitor.. These findings suggest that mutual upregulation of ET-1 and IL-25 takes place in the epidermis of AD, which may be a future target for antipruritic agents.

Topics: Animals; Dermatitis, Atopic; Disease Models, Animal; Endothelin-1; Gene Expression; Humans; Interleukin-17; Keratinocytes; MAP Kinase Signaling System; Mice; Phenotype; Receptor, Endothelin A; RNA, Messenger; Up-Regulation

In investigation were included 33 children with mild and moderate bronchial asthma of atopic geneses, average duration of the disease 3,5+/-1,9 years, average frequency of asthma attacks was less then once per month (night attacks 2-3 times per week), factors of initiation were dust and sharp smells. It was shown, that in atopic bronchial asthma in children, disbalance in endothelial system is developed, the content of endothelin-1, vasoconstrictor peptide of endotheliocytes, is increased by 64%. At the same time, coefficient of correlation between redox-potential NADP/NADPH and content of IgE decreases from 0,79 (p<0,01) in norm to 0,57 (p<0,05). Obtained data raises the issue of necessity of inclusion in the therapy of bronchial asthma the remedies which prevent bioenergetic failure.

Topics: Asthma; Child; Child, Preschool; Dermatitis, Atopic; Endothelin-1; Female; Humans; Hypoxia; Immunoglobulin A; Immunoglobulin E; Male; Oxidation-Reduction; Skin

Infants with severe atopic dermatitis (AD) sometimes have cold and pale fingers and toes as observed in patients with Raynaud-like phenomenon (RP). We tried to clarify the physiological mechanism of secondary RP in patients with AD. The correlation between serum endothelin-1 (ET-1) or nitrate (NO3) levels and the severity of AD was examined in 37 patients. As a result, RP was observed in 5 boys younger than 6 months of age and with severe AD. These 5 infants had high serum ET-1 levels. However, serum NO3 levels were only mildly elevated. These results suggest that secondary RP in AD may occur with elevated ET-1 caused by stressed and/or damaged endothelium in infants with severe AD.

Topics: Child, Preschool; Dermatitis, Atopic; Endothelin-1; Female; Humans; Infant; Male; Nitrates; Raynaud Disease

Various peptidases, including angiotensin-converting enzyme (ACE), inactivate some inflammatory peptides that are considered to influence the pathogenesis of atopic diseases. This enzyme is also involved in the conversion or activation of 2 bronchoconstriction mediators: angiotensin II from angiotensinogen and endothelin (ET), respectively.. We tested a hypothesis that asthma or other atopic diseases are associated with insertion/deletion ACE, M235T angiotensinogen, and TaqI ET-1 gene polymorphisms.. A case-control approach was used in the study. Healthy subjects (141 persons) were used as control subjects, and 231 patients with histories of atopic asthma, allergic rhinitis, atopic dermatitis, or a combination thereof were studied. ACE genotype was determined by PCR, angiotensinogen M235T and ET-1 by PCR, and restriction analysis by AspI and TaqI, respectively.. We found the significant association of the insertion/deletion polymorphism of the ACE, as well as that of M235T polymorphism of the angiotensinogen genes, with the group of patients with atopic diseases ( P =.0025 and P =.0204, respectively). No difference was proved for the intron 4 (position 8000) polymorphism in the ET-1 gene when comparing the atopic patients with the control group (P =.1774). A significant difference was found between groups of patients with both asthma and rhinitis and patients without both respiratory atopic diseases (P =.0033).. It follows that the examined polymorphisms in the genes for ACE, angiotensinogen, and ET-1 could participate in the etiopathogenesis of atopic diseases.

Topics: Adolescent; Adult; Alleles; Angiotensinogen; Asthma; Case-Control Studies; Dermatitis, Atopic; Endothelin-1; Female; Gene Frequency; Genotype; Humans; Hypersensitivity, Immediate; Male; Middle Aged; Mutation, Missense; Peptidyl-Dipeptidase A; Point Mutation; Polymerase Chain Reaction; Polymorphism, Genetic; Restriction Mapping; Rhinitis, Allergic, Seasonal