RÉSUMÉ
Galectin-9 is a member of the galectin family that has a wide spectrum of biological functions. Among them, galectin-9 has been known mainly as a potent chemoattractant for eosinophils. In addition, galectin-9 alters the T-cell balance by negatively regulating T-helper (Th)1 and Th17 cells, resulting in Th2 polarization. Atopic dermatitis (AD) is a skin allergic disease characterized by peripheral eosinophilia, mast cell activation and predominance of Th2 cells. To investigate possible roles of galectin-9 in AD, we measured serum galectin-9 levels in AD patients and investigated galectin-9 expression in lesional skin by immunohistochemistry. Serum galectin-9 levels in patients with AD were significantly higher than those in healthy controls and correlated with the Eczema Area and Severity Index. Serum galectin-9 levels were decreased after treatment, accompanied by improvement of skin lesions. Immunohistochemical study revealed that galectin-9 was expressed on epidermal keratinocytes and mast cells in lesional skin of AD. Our results suggest that elevated galectin-9 expression is associated with progression of AD and that galectin-9 could be a therapeutic target in AD.
Sujet(s)
Eczéma atopique/sang , Galectines/sang , Adulte , Études cas-témoins , Eczéma atopique/métabolisme , Femelle , Galectines/analyse , Humains , Kératinocytes/composition chimique , Mâle , Mastocytes/composition chimique , Indice de gravité de la maladieRÉSUMÉ
Depsipeptide (FK228), a histone deacetylase inhibitor, was recently approved for use in cutaneous T-cell lymphoma. Roxithromycin (RXM) is a macrolide antibiotic that can induce apoptosis of some T-cell lines. In this study, we investigated whether combination of FK228 and RXM had a synergistic inhibitory effect on cell survival of various lymphoma cells and which signaling pathway was affected by the drugs in the presence or absence of chemokines, which were reported to inhibit apoptosis of some tumor cells. FK228 and RXM additively decreased the number of HUT-78, Ki-JK and EL-4 lymphoma cells at doses over 50 nmol/L and 50 µmol/L, respectively. These drugs inhibited phosphorylation of Akt and extracellular signal-regulated kinase (ERK) of EL-4 cells in a dose-dependent manner. Significant association between ERK phosphorylation and cell number or annexin V(+) cells suggested that the ERK pathway may be critical for survival of EL-4 cells. Combination of 10 or 50 nmol/L of FK228 and 10 µmol/L of RXM decreased cell number of HUT78 and EL-4 compared to a single use of each drug. Our in vitro study suggested that combination of FK228 and RXM may be helpful for enhancing tumor killing effects. Although further study is necessary, this combination may be applicable to patients with cutaneous T-cell lymphoma in the future.
Sujet(s)
Antibactériens/usage thérapeutique , Depsipeptides/usage thérapeutique , Extracellular Signal-Regulated MAP Kinases/antagonistes et inhibiteurs , Lymphomes/traitement médicamenteux , Roxithromycine/usage thérapeutique , Animaux , Antibactériens/pharmacologie , Apoptose/effets des médicaments et des substances chimiques , Lignée cellulaire tumorale , Depsipeptides/pharmacologie , Tests de criblage d'agents antitumoraux , Humains , Souris , Roxithromycine/pharmacologieSujet(s)
Eczéma atopique/sang , Régulation de l'expression des gènes , Phosphodiesterases/sang , Prurit/sang , Adolescent , Adulte , Études cas-témoins , Enfant , Eczéma atopique/complications , Femelle , Humains , Hydrolyse , Mâle , Adulte d'âge moyen , Prurit/complications , Transduction du signal , Résultat thérapeutique , Jeune adulteRÉSUMÉ
Visfatin, a novel adipocytokine, is related with chronic inflammatory diseases, especially those characterized by T helper (Th)1-type immune responses. In this study, we examined serum visfatin levels in patients with atopic dermatitis (AD) or cutaneous T-cell lymphoma (CTCL), both of which are Th2-dominant diseases. Serum visfatin levels in patients with AD or advanced stage CTCL were significantly elevated compared to healthy controls. In CTCL patients, serum visfatin levels significantly decreased after treatment. Serum visfatin levels correlated with eosinophil counts in AD patients, whereas they correlated with the visual analogue scale itch scores and serum C-C motif ligand (CCL) 11 and CCL26 levels in CTCL patients. Visfatin expression by adipose tissue in lesional skin of AD and advanced stage CTCL was enhanced compared to that of healthy controls. These results suggest that visfatin may also be important in the development of Th2-dominant diseases as well as in Th1-type diseases.
Sujet(s)
Cytokines/sang , Eczéma atopique/enzymologie , Mycosis fongoïde/métabolisme , Nicotinamide phosphoribosyltransferase/sang , Syndrome de Sézary/métabolisme , Tumeurs cutanées/métabolisme , Tissu adipeux/enzymologie , Adulte , Sujet âgé , Hémogramme , Indice de masse corporelle , Études cas-témoins , Chimiokine CCL11/sang , Chimiokine CCL26 , Chimiokines CC/sang , Eczéma atopique/sang , Granulocytes éosinophiles , Femelle , Humains , Mâle , Adulte d'âge moyen , Mycosis fongoïde/anatomopathologie , Mycosis fongoïde/thérapie , Prurit/sang , Indice de gravité de la maladie , Syndrome de Sézary/anatomopathologie , Syndrome de Sézary/thérapie , Peau/enzymologie , Tumeurs cutanées/anatomopathologie , Tumeurs cutanées/thérapie , Jeune adulteRÉSUMÉ
BACKGROUND: Classically activated macrophages produce IL-12, IL-23, and TNF-α, whereas alternatively activated macrophages (M2 cells) produce IL-10 and express several receptors such as mannose receptor and CD163. Tumor-associated macrophages exhibit M2 phenotype, whose presence has been associated with poor prognosis in various tumors. OBJECTIVES: To investigate distribution of CD163(+) cells in lesional skin and serum levels of soluble CD163 (sCD163) in patients with cutaneous T cell lymphoma (CTCL), atopic dermatitis (AD), or psoriasis. METHODS: The numbers of CD163(+) and CD68(+) cells in lesional skin of CTCL, AD, or psoriasis, and in normal skin were examined by immunohistochemistry. Serum soluble CD163 (sCD163) levels were quantified by enzyme-linked immunosorbent assay. RESULTS: The numbers of CD163(+) cells in lesional skin of CTCL, AD, or psoriasis were significantly larger than in normal skin. In CTCL, the numbers of CD163(+) or CD68(+) cells increased as more tumor cells infiltrated and they decreased after treatment with topical steroid and ultraviolet light. Moreover, CTCL patients with an increased number of CD163(+) cells showed worse prognosis. Serum sCD163 levels in patients with CTCL, AD, or psoriasis were significantly higher than those in normal controls. In CTCL patients, serum sCD163 levels significantly correlated with serum soluble interleukin-2 receptor and CCL17 levels. In AD patients, serum sCD163 levels correlated with serum IgE levels. CONCLUSION: The numbers of CD163(+) cells in lesional skin and serum sCD163 levels were associated with disease progression of CTCL. Further study focusing on CD163(+) cells in CTCL lesional skin would be an interesting research field.
Sujet(s)
Antigènes CD/métabolisme , Antigènes de différenciation des myélomonocytes/métabolisme , Marqueurs biologiques tumoraux/métabolisme , Lymphome T cutané/immunologie , Macrophages/immunologie , Récepteurs de surface cellulaire/métabolisme , Tumeurs cutanées/immunologie , Peau/immunologie , Adulte , Sujet âgé , Antigènes CD/sang , Antigènes de différenciation des myélomonocytes/sang , Marqueurs biologiques tumoraux/sang , Chimiokine CCL17/sang , Eczéma atopique/sang , Eczéma atopique/immunologie , Évolution de la maladie , Test ELISA , Humains , Immunoglobuline E/sang , Immunohistochimie , Estimation de Kaplan-Meier , Lymphome T cutané/sang , Lymphome T cutané/mortalité , Lymphome T cutané/anatomopathologie , Lymphome T cutané/thérapie , Activation des macrophages , Macrophages/anatomopathologie , Adulte d'âge moyen , Phénotype , Psoriasis/sang , Psoriasis/immunologie , Récepteurs de surface cellulaire/sang , Récepteurs à l'interleukine-2/sang , Peau/anatomopathologie , Tumeurs cutanées/sang , Tumeurs cutanées/mortalité , Tumeurs cutanées/anatomopathologie , Tumeurs cutanées/thérapie , Résultat thérapeutique , Jeune adulteRÉSUMÉ
Dermatofibroma, also called cutaneous fibrous histiocytoma or sclerosing hemangioma, is a fairly common, benign cutaneous tumor. Polypoid dermatofibroma is an unusual and poorly recognized form of this entity. We describe a peculiar case of this variant presenting with a unique morphology characterized by a round flat shape with a slim pedicle, although its histopathological picture was rather typical of that of ordinary dermatofibroma.
Sujet(s)
Histiocytome fibreux bénin/anatomopathologie , Tumeurs cutanées/anatomopathologie , Sujet âgé , Femelle , Histiocytome fibreux bénin/chirurgie , Humains , Tumeurs cutanées/chirurgieSujet(s)
Interleukines/sang , Mycosis fongoïde/sang , Syndrome de Sézary/sang , Tumeurs cutanées/sang , Adulte , Sujet âgé , Eczéma atopique/sang , Humains , Adulte d'âge moyen , Mycosis fongoïde/anatomopathologie , Stadification tumorale , Indice de gravité de la maladie , Syndrome de Sézary/anatomopathologie , Tumeurs cutanées/anatomopathologie , Jeune adulteSujet(s)
Chimiokines CC/sang , Chimiokines CC/immunologie , Pemphigoïde bulleuse/immunologie , Pemphigoïde bulleuse/métabolisme , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Cloque/immunologie , Cloque/métabolisme , Cloque/anatomopathologie , Chimiokine CCL26 , Femelle , Humains , Mâle , Adulte d'âge moyen , Pemphigoïde bulleuse/anatomopathologieRÉSUMÉ
C-C chemokine receptor (CCR)10 is a specific receptor for chemokine ligand (CCL)27, a selective chemoattractant for skin-associated memory T cells to cutaneous sites. In melanoma, CCR10 increases the ability of neoplastic cells to grow, invade tissues, disseminate to lymph nodes, and escape the host immune responses. In this study, we investigated the expression of CCR10 and its ligand CCL27 in squamous cell carcinoma (SCC). CCR10 and CCL27 were expressed in SCC, actinic keratosis (AK), Bowen's disease, and seborrheic keratosis (predominantly prickle cell type), but not in seborrheic keratosis (predominantly basal cell type) and basal cell carcinoma. Furthermore, CCR10 and CCL27 were overexpressed in SCC relative to Bowen's disease, an early stage of SCC. Consistently, a human SCC cell line, A253 cells, and HaCaT cells exhibited CCL27 production that was strongly induced by tumor necrosis factor-α and interleukin-1ß. Finally, A253 cells expressed stronger intracellular CCR10 compared to HaCaT cells by flow cytometry. These results suggest that CCR10 and CCL27 overexpression in SCC is related to the progression of SCC and is useful for the diagnosis of SCC.
Sujet(s)
Carcinome épidermoïde/métabolisme , Chimiokine CCL27/métabolisme , Récepteurs CCR10/métabolisme , Tumeurs cutanées/métabolisme , Biopsie , Maladie de Bowen/immunologie , Maladie de Bowen/métabolisme , Maladie de Bowen/anatomopathologie , Carcinome basocellulaire/immunologie , Carcinome basocellulaire/métabolisme , Carcinome basocellulaire/anatomopathologie , Carcinome épidermoïde/immunologie , Carcinome épidermoïde/anatomopathologie , Lignée cellulaire tumorale , Régulation de l'expression des gènes tumoraux , Humains , Immunohistochimie , Interleukine-1 bêta/immunologie , Interleukine-1 bêta/métabolisme , Kératose actinique/immunologie , Kératose actinique/métabolisme , Kératose actinique/anatomopathologie , Kératose séborrhéique/immunologie , Kératose séborrhéique/métabolisme , Kératose séborrhéique/anatomopathologie , Peau/métabolisme , Peau/anatomopathologie , Tumeurs cutanées/immunologie , Tumeurs cutanées/anatomopathologie , Facteur de nécrose tumorale alpha/immunologie , Facteur de nécrose tumorale alpha/métabolismeRÉSUMÉ
BACKGROUND: ß7 Integrin, a cell adhesion molecule, is present in the form of α4ß7 integrin or αEß7 integrin. α4ß7 Integrin is expressed on most leucocytes and is essential for their migration to gut-associated lymphoid tissues by interacting with its primary ligand, mucosal addressin cell adhesion molecule-1, which is preferentially expressed in gut-associated lymphoid tissues. Although the importance of α4ß7 integrin in intestinal inflammation has been established, its role in cutaneous inflammation remains to be elucidated. OBJECTIVE: We sought to investigate the role of ß7 integrin in cutaneous inflammation. METHODS: We used a murine contact hypersensitivity model and examined the role of ß7 integrin by using ß7 integrin-deficient and αE integrin-deficient mice. RESULTS: ß7 Integrin-deficient mice, not αE integrin-deficient mice, are defective in contact hypersensitivity responses. ß7 Integrin deficiency does not affect irritant contact dermatitis. The distribution, migration, and function of antigen presenting cells from ß7 integrin-deficient mice are comparable to those from wild-type mice. Moreover, sensitized ß7 integrin-deficient T cells are able to respond to antigen stimuli in vitro and elicit contact hypersensitivity responses when directly injected into the skin. However, they are defective in reaching the skin under inflammatory conditions, resulting in reduced contact hypersensitivity responses when intravenously injected. Furthermore, intraperitoneal injection of anti-α4ß7 integrin neutralizing antibody elicit impaired contact hypersensitivity responses. CONCLUSION: α4ß7 Integrin contributes to contact hypersensitivity responses by regulating T-cell migration to inflammatory skin.
Sujet(s)
Eczéma de contact/immunologie , Intégrines/métabolisme , Peau/immunologie , Lymphocytes T/métabolisme , Transfert adoptif , Animaux , Anticorps bloquants/administration et posologie , Mouvement cellulaire/effets des médicaments et des substances chimiques , Mouvement cellulaire/génétique , Cellules cultivées , Eczéma de contact/traitement médicamenteux , Eczéma de contact/génétique , Immunité muqueuse/effets des médicaments et des substances chimiques , Intégrines/antagonistes et inhibiteurs , Intégrines/génétique , Intégrines/immunologie , Activation des lymphocytes/effets des médicaments et des substances chimiques , Activation des lymphocytes/génétique , Souris , Souris de lignée C57BL , Souris knockout , Peau/effets des médicaments et des substances chimiques , Peau/anatomopathologie , Lymphocytes T/effets des médicaments et des substances chimiques , Lymphocytes T/immunologie , Lymphocytes T/anatomopathologieRÉSUMÉ
The immunological significance of IL-27 has been reported and discussed in various Th1/Th17-mediated inflammatory diseases. However, its importance in psoriasis is unknown. We investigated pathophysiological roles of IL-27 in psoriasis in this study. Serum IL-27 levels in psoriatic patients were significantly higher than those in healthy controls, and correlated with disease severity and serum IFN-gamma levels. An immunohistochemical analysis revealed the infiltration of IL-27-secreting cells in the papillary dermis of psoriatic skin lesions but not in skin lesions with atopic dermatitis or normal skin. Furthermore, IL-27 alone greatly induced in vitro CXCL9, CXCL10, and CXCL11 production and tyrosine phosphorylation of signal transducer and activator of transcription 1 in normal human keratinocytes, while it suppressed the tumor necrosis factor-alpha-induced production of IL-1alpha and CCL20. These results indicate that IL-27 may promote the onset of psoriasis, while it may simultaneously attenuate the expanded inflammation in this disease. Our results implicate potential therapeutic effects of IL-27 for psoriasis.