ABSTRACT
BACKGROUND: Psoriasis is a chronic inflammatory skin disease that affects approximately 1~3% of the general population. OBJECTIVE: We performed cDNA microarray analysis with using the dendrimer labelling method to investigate the gene expression profile in the peripheral blood mononuclear cells (PBMCs) of psoriatic patients. METHODS: The peripheral blood mononuclear cells of 5 patients with psoriasis and 8 control subjects were used in the gene expression analyses of psoriasis. RESULTS: We identified 212 differentially expressed genes that showed at least a two-fold induction and/or reduction in psoriatic patients. Among those, 63 genes, including CD44, CD56 and IL7R, were induced, while 139 genes, including the sphingosine kinase 1 and p16-INK genes, were reduced in the psoriatic patients. CONCLUSION: We can speculate that these genes may have a role for the pathogenesis of psoriasis via their affecting different cellular functions. Our results suggest a possible mechanism by which activated immune cells migrate from the blood to the skin in psoriatic patients, and we provide novel putative targets for developing drugs to treat psoriasis
Subject(s)
Humans , Cell Adhesion , Dendrimers , Gene Expression , Oligonucleotide Array Sequence Analysis , Phosphotransferases , Phosphotransferases (Alcohol Group Acceptor) , Psoriasis , Skin , Skin Diseases , Sphingosine , TranscriptomeABSTRACT
In a previous search for the differentially expressed genes in keratinocyte differentiation, we identified neutrophil gelatinase-associated lipocalin (NGAL) as a calcium- induced gene. In this study, we further verified the expression of NGAL in cultured keratinocytes as well as in several skin diseases. Reverse transcription-polymerase chain reaction (RT-PCR), Western blot, and ELISA clearly showed that NGAL expression was markedly increased in calcium-induced keratinocyte differentiation in vitro. However, in our previous report, NGAL expression was not detected in normal skin tissue except for hair follicle by in situ hybridization and immunohistochemistry, indicating the difference of cell status between in vitro and in vitro conditions. Interestingly, NGAL expression was highly increased in psoriasis-like inflammatory disorders (lichen planus and pityriasis rubura pilaris) and skin cancers (keratoacanthoma and squamous cell carcinoma), implying that NGAL may be related with the epidermal hyperplasia. Collectively, these results reveal the potential importance of NGAL in the maintenance of skin homeostasis.
Subject(s)
Humans , Acute-Phase Proteins/biosynthesis , Calcium/metabolism , Cell Differentiation , Culture Media , Culture Media, Conditioned , Enzyme-Linked Immunosorbent Assay , Gene Expression Regulation , Homeostasis , Keratinocytes/enzymology , Lipocalins/biosynthesis , Models, Biological , Proto-Oncogene Proteins/biosynthesis , Psoriasis/enzymology , Reverse Transcriptase Polymerase Chain Reaction , Skin/metabolism , Skin Neoplasms/enzymologyABSTRACT
Cancer cachexia, characterized by weight loss and progressive tissue wasting, has been postulated to be mediated by cytokines. This study was conducted to evaluate the effect of Korean Traditional Medicine (KTM ; mokhyang, jisil, osooyu) mixture on food intake, blood cytokines level and blood nutrients status of the cachexia induced-mice. Thirty male Balb/c mice aged 6-8 weets were blocked into 3 groups that were Normal (no colon26 cells) Control (colon 26 cells) and KTM (colon26 cells + KTM extract mixture) group. In Control and KTM groups, murine adenocarcinoma colon 26 cells were injected subcutaneously to induce cachexia. KTM mice were given 200 ul KTM extract mixture (7%) per day. Half of each groups were sacrificed at the 14 th day to see serum cytokines & nutrients and the others were fed until almost of control group died to see life span. food intake and body weight were decreased significantly in cachexia induced groups. Tumor weight of KTM group was significantly lower than control group. Serum cytokines (IL-1beta and TNF-alpha) level of cachexia induced groups were increased than those of normal group, and those of KTM group were significantly lower than the level of control group. Total serum protein and serum albumin were higher in KTM group than other groups. TG and fatty acid were lower in cachexia induced groups than normal group. HDL-cholesterol in serum was increased in KTM group. Effect of oral administration of KTM extract mixture on survival time of colon26 bearing mice showed extension of the life span. Overall, this study showed that KTM (mokhyang, jisil, osooyu) extract mixture inhibited the growth of cancer cell, changed the secretion of cytokines induced by colon26 adenocarcinoma in mice, and changed nutrition metabolism.
Subject(s)
Animals , Humans , Male , Mice , Adenocarcinoma , Administration, Oral , Body Weight , Cachexia , Colon , Cytokines , Eating , Interleukin-1beta , Medicine, East Asian Traditional , Medicine, Korean Traditional , Metabolism , Serum Albumin , Tumor Burden , Tumor Necrosis Factor-alpha , Weight LossABSTRACT
The Korean traditional medicinal (KTM) herbs such as Angelicae gigantis, Rehmannia glutinosa, Paeoniae lactiflora, Cnidii officinale, Salviae miltiorrhizae, and Millettia reticulata, and prescribed formula Samultang, and Bohyultang improve the function of the hematopoietic system and nourishing the body to promote health. However, there are limited scientific background on the mode of action of these medicine. To understand the diverse actions following traditional medicine stimulation, we determined the production of hematopoietic cytokine, thrombopoietin, stem cell factor, and interleukin-3 (IL-3) in KlM treated bone marrow cells. When bone marrow cells were treated with KTM, the expression of hematopoietic cytokine were increased in RT-PCR and ELISA analysis. Furthermore, when the bone marrow cells were separated into adherent celis and suspension cells and were treated with KTM, we found the increase of TPO gene expressions in suspension cells. Meanwhile, other hematopoietic cytokine gene expression in bone marrow cells was higher as whole than when adherent cells and suspension cells was separated. Therefore, we could know the interaction of two cells that increases the cytokine expression. These results suggest that KTM has hematopoietic effects through increasing the production of cytokine.
Subject(s)
Angelica , Bone Marrow Cells , Enzyme-Linked Immunosorbent Assay , Gene Expression , Hematopoiesis , Hematopoietic System , Interleukin-3 , Medicine, Korean Traditional , Medicine, Traditional , Millettia , Paeonia , Rehmannia , Salvia , Stem Cell Factor , ThrombopoietinABSTRACT
Recently, we found that the Korean traditional medicine could enhance the expression of some cytokine in murine bone marrow cell culture. To understand the mode of actions of the traditional medicine, we examined the pattern of protein phosphorylation in bone marrow cells treated with Korean traditional medicine. When bone marrow cells were treated with Korean traditional medicine, the phosphorylation of p45, p50, p84/p91 kinase was observed, and gene expression of TPO and SCF was related to p45 and p91. It had been reported that TPO, SCF, IL-3 and GM-CSF gene expression transmits signal through the JAK-STAT pathway. Molecular involvement of JAK-STAT in signal induced by Korean traditional medicine was analyzed by anti-JAK and anti-STAT-1 Ab. To analyze the transcriptional factor that promotes the cytokine gene expression by the stirnulation of Korean traditional medicine, GAS and NF-B binding activity was analyzed by EMSA. We found the increase in NF-B at SMT and BHT. Therefore, we conclude that the cytokine gene expression induced by Korean traditional medicine was mediated by the JAK-STAT pathway and by the combination of GAS and NF-kB.