OBJECTIVES: This study aimed to determine whether a correlation existed between CXC chemokine ligand 10 (CXCL10)-CXC chemokine receptor 3 (CXCR3) and CC chemokine ligand 17 (CCL17)-CC chemokine receptor 4 (CCR4) in the pathogenesis of oral lichen planus (OLP). METHODS: Peripheral blood of OLP patients (non-erosive and erosive groups) and healthy controls were collected, and T cells were isolated and purified. T cells were co-cultured with three groups: blank, anti-CXCR3, and anti-CCR4. CXCR3 and CCR4 expression were detected by flow cytometry, and CXCL10 and CCL17 were detected by enzyme-linked immunosorbent assay, respectively. RESULTS: The purities of T cells were all >95% in the three groups ( CONCLUSIONS Two axes interact with each other in the pathogenesis of OLP and may play different roles in its occurrence and development.
Chemokine CCL17 ; Chemokine CXCL10 ; Humans ; Lichen Planus, Oral ; Ligands ; Receptors, CCR4 ; Receptors, CXCR3

BACKGROUND: The canonical Wnt/β-catenin signaling pathway is a fundamental regulatory system involved in various biological events. ICG-001 selectively blocks the interaction of β-catenin with its transcriptional co-activator cyclic AMP response element-binding protein (CBP). Recent studies have provided convincing evidence of the inhibitory effects of ICG-001 on Wnt-driven disease models, such as organ fibrosis, cancer, acute lymphoblastic leukemia, and asthma. However, the effects of ICG-001 in atopic dermatitis (AD) have not been investigated. OBJECTIVE: To investigate whether β-catenin/CBP-dependent signaling was contributed in the pathogenesis of AD and ICG-001 could be a therapeutic agent for AD. METHODS: We examined the effects of ICG-001 in an AD-like murine model generated by repeated topical application of the hapten, oxazolone (Ox). ICG-001 or vehicle alone was injected intraperitoneally every day during the development of AD-like dermatitis arising from once-daily Ox treatment. RESULTS: Ox-induced AD-like dermatitis characterized by increases in transepidermal water loss, epidermal thickness, dermal thickness accompanied by increased myofibroblast and mast cell counts, and serum levels of thymic stromal lymphopoietin and thymus and activation-regulated chemokine, and decreases in stratum corneum hydration, were virtually normalized by the treatment with ICG-001. Elevated serum levels of periostin tended to be downregulated, without statistical significance. CONCLUSION: These results suggest that β-catenin/CBP-dependent signaling might be involved in the pathogenesis of AD and could be a therapeutic target.
Animals ; Asthma ; Chemokine CCL17 ; Cyclic AMP Response Element-Binding Protein ; Cyclic AMP ; Dermatitis ; Dermatitis, Atopic ; Fibrosis ; Mast Cells ; Mice ; Myofibroblasts ; Oxazolone ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Water

BACKGROUND: Atopic dermatitis (AD) in infants is often related to food allergies (FA). The beneficial effects of lactic acid bacteria towards allergic diseases have been reported, but there are few reports on their effect and preferable dosages on AD in young children with concomitant FA. OBJECTIVE: To examine additional effects of two different dose of paraprobiotic Lactobacillus acidophilus L-92 (L-92) on the clinical treatment in young children afflicted by AD with diagnosed or suspected FA. METHODS: Fifty-nine AD young children from 10 months to 3 years old, with FA or who had not started to ingest specific food(s) because of high specific IgE levels, were recruited and randomly allocated into L-92 group (daily intake of 20 mg L-92/day) and placebo group. Participants were given test sample with conventional treatment for AD over a 24-week period. The severity of eczema was evaluated using SCORing Atopic Dermatitis (SCORAD) index before intervention, and at 4, 12, and 24 weeks after intervention. RESULTS: After 24 weeks of intervention, a significant decrease in SCORAD was observed only in the L-92 group when compared with the baseline values. Significant decreases in thymus and activation-regulated chemokine (TARC) and total IgE were also detected 24 weeks after intake in the L-92 group compared with the placebo group. CONCLUSION: It was suggested that intake of sufficient amounts of L-92 works as an adjunctive treatment of young children afflicted by AD with diagnosed or suspected FA.
Bacteria ; Chemokine CCL17 ; Child ; Dermatitis, Atopic ; Eczema ; Food Hypersensitivity ; Humans ; Immunoglobulin E ; Infant ; Lactic Acid ; Lactobacillus acidophilus ; Lactobacillus

BACKGROUND: Empirical evidences for efficacy of hot spring (HS) water in inflammatory skin disorders have not been substantiated with sufficient, immunological “hard evidence”. Mageumsan HS water, characterized by its weakly-alkaline properties and low total dissolved solids content, has been known to alleviate various immune-inflammatory skin diseases, including atopic dermatitis (AD). OBJECTIVE: The trial attempted to quantitatively analyze in vitro expression levels of chemical mediators in cutaneous inflammation from HaCaT cell line treated with Mageumsan HS, and suggest the likely mode of action through which it exerts the apparent anti-inflammatory effects in AD. METHODS: Using membrane-based human antibody array kit, customized to include 30 different, keratinocyte-derived mediator proteins, their expression levels (including interleukin [IL]-1, IL-6, IL-8, thymic stromal lymphopoietin, thymus and activation-regulated chemokine, and granulocyte macrophage colony-stimulating factor) were assessed in vitro. Selected key proteins were further quantified with enzyme-linked immunosorbent assay. RESULTS: There was a clear pattern of overall suppression of the mediators, especially those noted for their pro-inflammatory role in AD (monocyte chemoattractant protein [MCP]-1, regulated on activation, normal T cell expressed and secreted, cutaneous T-cell-attracting chemokine, Eotaxin, and macrophage inflammatory protein-1α, etc.). Also, reduced expression of involucrin and cytokeratin 1 was also reduced in the HS-treated group. CONCLUSION: The present study has shown that Mageumsan HS water may exert its effects on inflammatory skin disorders through regulation of proinflammatory cytokines. These evidences are to be supported with further future investigations to elucidate immunological mechanism behind these beneficial effects of HS water in the chronically inflamed skin of AD.
Cell Line ; Chemokine CCL17 ; Chemokine CCL27 ; Cytokines ; Dermatitis, Atopic ; Enzyme-Linked Immunosorbent Assay ; Granulocytes ; Hot Springs* ; Humans ; In Vitro Techniques* ; Inflammation ; Interleukin-6 ; Interleukin-8 ; Interleukins ; Keratins ; Macrophages ; Protein Array Analysis* ; Skin ; Skin Diseases ; Water

Atopic dermatitis (AD) results from gene and environment interactions that lead to a range of immunological abnormalities and breakdown of the skin barrier. Protease-activated receptor 2 (PAR2) belongs to a family of G-protein coupled receptors and is expressed in suprabasal layers of the epidermis. PAR2 is activated by both trypsin and a specific agonist peptide, SLIGKV-NH₂ and is involved in both epidermal permeability barrier homeostasis and epithelial inflammation. In this study, we investigated the effect of lobaric acid on inflammation, keratinocyte differentiation, and recovery of the skin barrier in hairless mice. Lobaric acid blocked trypsin-induced and SLIGKV-NH₂-induced PAR2 activation resulting in decreased mobilization of intracellular Ca²⁺ in HaCaT keratinocytes. Lobaric acid reduced expression of interleukin-8 induced by SLIGKV-NH₂ and thymus and activation regulated chemokine (TARC) induced by tumor necrosis factor-a (TNF-α) and IFN-γ in HaCaT keratinocytes. Lobaric acid also blocked SLIGKV-NH₂-induced activation of ERK, which is a downstream signal of PAR2 in normal human keratinocytes (NHEKs). Treatment with SLIGKV-NH₂ downregulated expression of involucrin, a differentiation marker protein in HaCaT keratinocytes, and upregulated expression of involucrin, transglutamase1 and filaggrin in NHEKs. However, lobaric acid antagonized the effect of SLIGKV-NH₂ in HaCaT keratinocytes and NHEKs. Topical application of lobaric acid accelerated barrier recovery kinetics in a SKH-1 hairless mouse model. These results suggested that lobaric acid is a PAR2 antagonist and could be a possible therapeutic agent for atopic dermatitis.
Animals ; Chemokine CCL17 ; Dermatitis, Atopic ; Epidermis ; GTP-Binding Proteins ; Homeostasis ; Humans ; Inflammation ; Interleukin-8 ; Keratinocytes ; Kinetics ; Mice ; Mice, Hairless ; Necrosis ; Permeability ; Receptor, PAR-2 ; Skin* ; Trypsin

Fucoidan, a sulfated polysaccharide is found in several types of edible brown algae. It has shown numerous biological activities; however, the molecular mechanisms on the activity against atopic dermatitis have not been reported yet. We now examined the effects of fucoidan on chemokine production co-induced by TNF-alpha/IFN-gamma, and the possible mechanisms underlying these biological effects. Our data showed that fucoidan inhibited the TNF-alpha/IFN-gamma-induced production of thymus and activation-regulated chemokine (TARC) and macrophagederived chemokine (MDC) mRNA in human keratinocytes HaCaT cells. Also, fucoidan suppressed phosphorylation of nuclear factor kappa B (NF-kappaB) and activation of signal transducer and activator of transcription (STAT)1 in a dose-dependent manner. In addition, fucoidan significantly inhibited activation of extracellular-signal-regulated kinases (ERK) phosphorylation. These data indicate that fucoidan shows anti-inflammatory effects by suppressing the expression of TNF-alpha/IFN-gamma-induced chemokines by blocking NF-kappaB, STAT1, and ERK1/2 activation, suggestive of as used as a therapeutic application in inflammatory skin diseases, such as atopic dermatitis.
Chemokine CCL17 ; Chemokines ; Dermatitis, Atopic ; Humans* ; Keratinocytes* ; NF-kappa B* ; Phaeophyta ; Phosphorylation ; Phosphotransferases ; RNA, Messenger ; Skin Diseases ; STAT1 Transcription Factor ; Transducers

OBJECTIVETo study the association of single nucleotide polymorphisms (SNPs, rs223895 and rs223899) in TARC/CCL17 gene with Kawasaki disease (KD) and its clinical characteristics in Han children from Central China.

METHODSA case-control study was performed on 218 children with KD and 248 normal control children. The genotypes of SNPs (rs223895 and rs223899) in TARC/CCL17 gene were determined by polymerase chain reaction-restriction fragment length polymorphism. The association between the SNPs in TARC/CCL17 gene and the clinical characteristics of KD was assessed.

RESULTSThere were significant differences in the genotype (CC, CT, TT) and allele frequencies of SNP rs223895 between children with KD and controls (P<0.05), and C allele was a risk factor (OR=1.397). However, no significant differences were found between the two groups in the genotype and allele frequencies of SNP rs223899. Compared with those with other genotypes (CT+TT) of SNP rs223895, patients with CC genotype had significantly lower hemoglobin (Hb) and albumin (Alb) levels (P<0.05) and a significantly higher erythrocyte sedimentation rate (ESR) (P<0.05).

CONCLUSIONSThe SNP rs223895 in TARC/CCL17 gene is associated with the susceptibility to KD, and C allele is a risk factor. Moreover, SNP rs223895 may influence the levels of Hb, Alb, and ESR.

Chemokine CCL17 ; genetics ; Child ; Child, Preschool ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Infant ; Male ; Mucocutaneous Lymph Node Syndrome ; genetics ; Polymorphism, Single Nucleotide

BACKGROUND: CC chemokine ligand 17 (CCL17) and CCL22 are the functional ligands for CCR4. We previously reported that inhibitors of nuclear factor-kappa B and p38 mitogen-activated protein kinase (p38 MAPK), but not of extracellular signal-related kinase (ERK), inhibited tumor necrosis factor (TNF)-alpha- and interferon (IFN)-gamma-induced production of CCL17 by the human keratinocyte cell line, HaCaT. Further, an inhibitor of epidermal growth factor receptor (EGFR) enhanced the CCL17 production by these keratinocytes. OBJECTIVE: To identify the mechanism underlying CCL22 production by HaCaT cells. METHODS: We investigated the signal transduction pathways by which TNF-alpha and IFN-gamma stimulate HaCaT cells to produce CCL22 by adding various inhibitors. RESULTS: TNF-alpha- and IFN-gamma-induced CCL22 production was inhibited by PD98059, PD153035, Bay 11-7085, SB202190, c-Jun N-terminal kinase (JNK) inhibitor II, and Janus kinase (JAK) inhibitor 1. CONCLUSION: Our results indicate that CCL22 production in HaCaT cells is dependent on ERK, EGFR, p38 MAPK, JNK, and JAK and is mediated by different signal pathways from those regulating CCL17 production. Altogether, our previous and present results suggest that EGFR activation represses CCL17 but enhances CCL22 production by these cells.
Bays ; Cell Line ; Chemokine CCL17 ; Chemokine CCL22 ; Humans ; Interferons ; JNK Mitogen-Activated Protein Kinases ; Keratinocytes* ; Ligands ; p38 Mitogen-Activated Protein Kinases ; Phosphotransferases ; Protein Kinases ; Receptor, Epidermal Growth Factor ; Signal Transduction ; Tumor Necrosis Factor-alpha

Citrus fruit contain various flavonoids that have multiple biological activities. However, the content of these flavonoids are changed during maturation and immature Citrus is known to contain larger amounts than mature. Chemokines are significant mediators for cell migration, while thymus and activation-regulated chemokine (TARC/CCL17) and macrophage-derived chemokine (MDC/CCL22) are well known as the typical inflammatory chemokines in atopic dermatitis (AD), a pruritic and chronic inflammatory skin disease. We reported recently that the EtOH extract of immature Citrus unshiu inhibits TARC and MDC production. Therefore, we investigated the activity of flavonoids contained in immature Citrus on TARC and MDC levels. As a result, among the various flavonoids, quercetagetin has stronger inhibitory effects on the protein and mRNA expression of TARC and MDC than other flavonoids. Quercetagetin particularly has better activity on TARC and MDC level than quercetin. In HPLC analysis, the standard peak of quercetagetin matches the peaks of extract of immature C. unshiu. This suggests that quercetagetin is an anti-inflammatory component in immature C. unshiu.
Cell Movement ; Chemokine CCL17 ; Chemokine CCL22 ; Chemokines ; Chromatography, High Pressure Liquid ; Citrus* ; Dermatitis, Atopic ; Flavonoids ; Humans* ; Keratinocytes* ; Quercetin ; RNA, Messenger ; Skin Diseases

PURPOSE: Atopic dermatitis may impair quality of life and lead to attention deficit-hyperactivity disorder (ADHD). Thymus and activation-regulated chemokine (TARC)/CCL17 may serve as a new biomarker for atopic dermatitis. We investigated the relationship between TARC and the severity of atopic dermatitis, quality of life, and ADHD. METHODS: A total of 249 preschool children who had atopic dermatitis were enrolled. Parents of the patients filled out a questionnaire on the past history of allergic diseases, quality of life, and ADHD. In each patient, total immunoglobulin (Ig) E and specific IgE to nine foods and inhalant allergens, total eosinophil counts, and TARC levels were measured. We evaluated the severity of atopic dermatitis by using the scoring atopic dermatitis (SCORAD) score and divided the patients into three groups; mild (<15), moderate (15 to 40), and severe (>40). RESULTS: In a total of 249 children, 222 children (89.2%) had a history of atopic dermatitis. Children with allergic sensitization had a higher SCORAD score, total IgE levels, and total eosinophil counts, but not TARC levels. Three groups by the SCORAD score showed significant differences in quality of life index and TARC levels but not in ADHD index. TARC level was correlated with the SCORAD score, but not with the quality of life index and ADHD index. The SCORAD score was correlated with the quality of life index but not with the ADHD index. CONCLUSION: Serum TARC levels may be associated with the severity of atopic dermatitis but not with the degree of quality of life and ADHD. Disease severity of atopic dermatitis in preschool children may be associated with the degree of quality of life but not with the level of ADHD.
Allergens ; Attention Deficit Disorder with Hyperactivity ; Chemokine CCL17 ; Child ; Child, Preschool ; Dermatitis, Atopic ; Eosinophils ; Humans ; Immunoglobulin E ; Immunoglobulins ; Parents ; Quality of Life ; Surveys and Questionnaires ; Thymus Gland