Biomedical subjects

Ming-Shi Chang

Publications and source records attributed to Ming-Shi Chang.

13 recordsLinked to original sources

PubMed2006

Tissue microarray analysis of interleukin-20 expression.

Knowledge about the biological functions and clinical implications of interleukin (IL)-20, a recently discovered cytokine in the IL-10 family, is still incomplete. Our aim was to determine the distribution of IL-20 expression and to delineate the cell types that express IL-20 in healthy and neoplastic tissue, because this information will significantly affect the exploration of its pathophysiological roles. We used tissue microarray technology and an immunohistochemical survey using an anti-IL-20 monoclonal antibody to examine IL-20 expression in 36 non-neoplastic and 14 neoplastic tissues. IL-20 protein was positively stained in 30 non-neoplastic tissue types and five major cell types: epithelial cells, myoepithelial cells, endothelial cells, macrophages, and skeletal muscle cells. We also found that several types of tumor cells stained positive for IL-20, especially in squamous cell carcinoma of the skin, tongue, esophagus, and lung. Our data provide valuable references for further investigation of the biological functions and clinical implications of IL-20 in humans.

Gene Expression Profiling↗

PubMed2006

IL-20 is expressed in atherosclerosis plaques and promotes atherosclerosis in apolipoprotein E-deficient mice.

OBJECTIVE: Atherosclerosis is a chronic inflammatory disease with immune cell infiltration. Various cytokines and chemokines have been characterized as pro- or antiatherogenic factors. Interleukin-20 (IL-20) belongs to the IL-10 family and is a proinflammatory cytokine involved in the pathogenesis of psoriasis. However, the association between IL-20 and atherosclerosis is undetermined. Therefore, we sought to investigate whether IL-20 is associated with atherosclerosis. METHODS AND RESULTS: We examined the expression of IL-20 and its receptor complex IL-20R1/IL-20R2 in atherosclerotic lesions of humans and mice using immunohistochemical staining. IL-20 was expressed in macrophage-rich areas. Both IL-20 and IL-20R1/IL-20R2 were expressed by endothelial cells lining the intimal microvessels, vasa vasorum, but rarely in nonatherosclerotic arteries. We used reverse-transcription polymerase chain reaction to analyze gene expression. IL-20 transcripts increased in hypoxic monocytes and monocytes treated with oxidized low-density lipoprotein. The expression of IL-20R1 and IL-20R2 was also upregulated by human umbilical vein endothelial cells in response to hypoxic treatment. Incubating IL-20 with human umbilical vein endothelial cells upregulated CXCL9 and CXCL11 transcripts. Furthermore, in vivo administration of IL-20 expression vector using intramuscular electroporation promoted atherosclerosis in apolipoprotein E-deficient mice. CONCLUSIONS: Our data suggest that IL-20 is a proatherogenic cytokine that contributes to the progression of atherosclerosis.

Animals↗

PubMed2006

IL-20: biological functions and clinical implications.

IL-20 belongs to the IL-10 family and plays a role in skin inflammation and the development of hematopoietic cells. Little is known about its other biological functions and clinical implications, however. Updated information about IL-20, such as its identification, expression, receptors, signaling, biological activities, and potential clinical implications, is illustrated in this review based on our research and on data available in the literature. Our studies of IL-20 show that it is a pleiotropic cytokine with potent inflammatory, angiogenic, and chemoattractive characteristics. Inflammation and angiogenesis are essential for the pathogenesis of rheumatoid arthritis and atherosclerosis. Based on in vitro data and clinical samples, we demonstrated that IL-20 is involved in the diseases of rheumatoid arthritis and atherosclerosis. In addition, we found in our studies that IL-20 signaled through different molecules in several cells. The present review presents the clinical implications of IL-20 in rheumatoid arthritis and atherosclerosis. It may provide new therapeutic options in the future.

Amino Acid Sequence↗

PubMed2006

Promoter analysis of interleukin 19.

Interleukin (IL)-19 belongs to the IL-10 family which includes IL-19, IL-20, IL-22, AK155, and MDA-7. IL-10 is a potent immunomodulatory cytokine with implications for pathogenesis in various autoimmune diseases. Polymorphism of the IL-10 promoter region correlates with disease outcome. To understand the gene regulation of IL-19, we analyzed the IL-19 promoter region. A regulatory region (PE), 148bp upstream of exon 1 of IL-19 and linked to a luciferase reporter gene, supported luciferase activity 13 times greater than that supported by a negative promoterless control. An electrophoretic mobility shift assay (EMSA) showed specific binding sites for the transcription factors of the oligonucleotides PE1 (-148 to -98) derived from PE. We identified the sequence TGTGGT (-142 to -138) on PE1 as the binding site for the transcription factor AML1, and crucial for the promoter activity of IL-19 because substituting 1bp in the PE region (-139G-->T) abolished IL-19 promoter activity.

Animals↗

PubMed2006

Function of interleukin-20 as a proinflammatory molecule in rheumatoid and experimental arthritis.

OBJECTIVE: The pathogenesis of rheumatoid arthritis (RA) reflects an ongoing imbalance between proinflammatory and antiinflammatory cytokines. Interleukin-20 (IL-20) has proinflammatory properties for keratinocytes. In this study, we sought to determine whether IL-20 is involved in RA. METHODS: We analyzed IL-20 levels in synovial fluid from RA patients. IL-20 and its receptors were detected in RA synovial fibroblasts (RASFs), using immunohistochemical staining. The effect of IL-20 on endothelial cells, neutrophils, and RASFs was investigated using MTT and migration assays. The expression of IL-20 and its receptors in healthy rats and in rats with collagen-induced arthritis (CIA) was also analyzed. Soluble IL-20 receptor type I (sIL-20RI) or sIL-20RII was administered to rats with CIA by intramuscular electroporation, and the severity of arthritis was monitored. RESULTS: RA patients expressed significantly higher levels of synovial fluid IL-20 than did the rheumatic disease controls. IL-20 and its receptors were expressed in the synovial membranes and RASFs. IL-20 induced RASFs to secrete monocyte chemoattractant protein 1, IL-6, and IL-8, and it promoted neutrophil chemotaxis, RASF migration, and endothelial cell proliferation. Both IL-20 and IL-20RI were up-regulated in the rat CIA model. In vivo, electroporated sIL-20RI plasmid DNA decreased the severity of arthritis in the rats with CIA. CONCLUSION: IL-20 was up-regulated in the synovial fluid of RA patients and acted as a chemokine that attracted the migration of neutrophils and RASFs in vitro. The rat CIA model demonstrated that IL-20 was involved in the pathogenesis of arthritis, because sIL-20RI significantly reduced arthritis in rats with CIA. Thus, IL-20 may modulate the incidence and severity of arthritis and play important roles at local sites of inflammation.

Animals↗

PubMed2006

Induction of interleukin-19 and interleukin-22 after cardiac surgery with cardiopulmonary bypass.

BACKGROUND: Interleukin (IL)-19, IL-20, and IL-22, three novel cytokines in the IL-10 family, have recently been discovered. The biological functions and clinical implications of these cytokines are not clear. We aimed to analyze if serum levels of these cytokines were altered in inflammatory responses of postoperative cardiopulmonary bypass (CPB) and investigate the molecular mechanism involved in cytokine induction. METHODS: Twenty-five patients undergoing elective aortic-coronary bypass grafting with CPB were enrolled in this study. Blood samples withdrawn at (T1) before anesthesia, (T2) CPB start, (T3) CPB end, (T4) 4 hours post-CPB, (T5) 8 hours post-CPB, (T6) 12 hours post-CPB, (T7) 24 hours post-CPB, and (T8) 48 hours post-CPB were assayed for IL-6, IL-10, IL-19, IL-20, IL-22, and tumor necrotic factor-alpha (TNF-alpha). Transcripts of IL-19, IL-20, and IL-22 from monocytes were analyzed. In vitro, levels of IL-19, IL-20, and IL-22 production in monocytes incubated with IL-6 and TNF-alpha were determined. RESULTS: The serum levels of IL-19 and IL-22 significantly increased at T3, peaked at T5, and remained increased at T8 (p<0.001). Induction of IL-19 and IL-22 was concomitant with the change in IL-10, IL-6, and TNF-alpha levels. Interleukin-19, IL-20, and IL-22 transcripts in monocytes from patients increased after CPB. In vitro experiments showed that IL-6 and TNF-alpha upregulated IL-19 protein expression in monocytes. CONCLUSIONS: Serum IL-19 and IL-22 were induced in cardiac surgery with CPB and concomitant with induction of IL-6 and TNF-alpha. The IL-19 and these proinflammatory cytokines may interactively contribute to systemic inflammatory responses after CPB.

Aged↗

PubMed2005

Detection of IL-20 and its receptors on psoriatic skin.

The aim of this study was to investigate the expression of interleukin-20 (IL-20) and its receptors on psoriatic skin by immunohistochemical analysis and to evaluate the correlation of CD8-positive T lymphocytes with epidermal proliferation. Overexpression of IL-20 and its receptors was detected in the keratinocytes of the lesional skin of psoriasis and spongiotic dermatitis. The expression pattern of IL-20 spreads throughout the whole layer of epidermis, while IL-19 was expressed in up to three or four layers suprabasally. The serum level of IL-20 in psoriatic patients was significantly lower than that in healthy controls. IL-20 upregulated KGF transcripts on CD8-positive T cells. We hypothesize that overexpression of IL-20 is correlated with keratinocyte proliferation that acts through their receptor complex expressed by keratinocytes themselves. Furthermore, IL-20 can stimulate CD8-positive lymphocytes to produce KGF, which may contribute to sustaining the hyperproliferative status of the keratinocytes.

CD8-Positive T-Lymphocytes↗

PubMed2005

IL-24 inhibits the growth of hepatoma cells in vivo.

The interleukin (IL)-24/melanoma differentiation associated gene-7 (mda-7) is a member of the IL-10 cytokine family. Introduction of the IL-24 gene into a variety of cancer cells suppresses their growth. It has not been shown, however, whether IL-24 can suppress the growth of hepatoma cells. The purpose of this study was to determine whether the mouse (m)IL-24 gene would suppress hepatoma cells in vivo after being delivered via intramuscular electroporation. After mice were given a subcutaneous dorsal injection of ML-1 hepatoma cells, the mIL-24 gene was delivered and suppressed tumor growth. On day 140, 60% of the mIL-24-treated mice (n=10) and 0% (n=10) of the untreated control mice had survived. We also generated a mouse-hepatoma model by injecting ML-1 cells into the spleen, which resulted in tumor metastasis in the liver. Intramuscular electroporation of mIL-24 also inhibited hepatoma-cell growth in the liver. On day 50, 90% of the experimental mice (n=10) and 40% (n=10) of the control mice had survived. Liver tumors in surviving experimental mice were 50% smaller than those in control mice. IL-24 also inhibited tumor vascularization. These results suggest that IL-24 has potential therapeutic value for hepatoma

Animals↗

PubMed2005

Interleukin-19 upregulates keratinocyte growth factor and is associated with psoriasis.

BACKGROUND: Interleukin (IL)-19, a member of the IL-10 family, signals through the IL-20R1/IL-20R2 heterodimer, which is shown to be involved in abnormal keratinocyte differentiation and proliferation. Little is known about its in vitro biological functions or its role in psoriasis. OBJECTIVES: To investigate the role of IL-19 in the psoriatic process. METHODS: The expression of keratinocyte growth factor (KGF) transcripts was measured by polymerase chain reaction in CD8+ T cells treated with IL-19. Next, we developed monoclonal and polyclonal antibodies to measure the levels of IL-19 in the sera of patients with psoriasis and healthy volunteers using an enzyme-linked immunosorbent assay. In addition, we performed immunohistochemical staining on psoriatic skin and normal controls. RESULTS: We found that IL-19 upregulated KGF transcripts on CD8+ T cells. Patients with psoriasis had a lower level of IL-19 in serum than healthy volunteers. The difference between these two groups was statistically significant (P < 0.05). IL-19 expression was seen in basal and suprabasal keratinocytes in a continuous pattern, and was increased in psoriatic epidermis. CONCLUSIONS: These results suggest that IL-19 plays a role in the complex pathological cytokine network in psoriasis.

CD8-Positive T-Lymphocytes↗

PubMed2004

IL-19 induced Th2 cytokines and was up-regulated in asthma patients.

IL-19 belongs to the IL-10 family, which includes IL-10, IL-19, IL-20, IL-22, melanoma differentiation-associated gene-7 (IL-24), and AK155 (IL-26). IL-10 has been shown to inhibit allergen-induced airway hyperreactivity and inflammation. To determine whether IL-19 was also associated with asthma, we used ELISA to analyze the serum level of IL-19 in patients with asthma and found that their serum IL-19 levels were twice those of healthy controls. Patients with a high level of IL-19 also had high levels of IL-4 and IL-13. In a dust mite-induced murine model of asthma, we found that IL-19 level in asthmatic BALB/cJ mice was also twice that of healthy control mice. IL-19 transcript was also induced in the lungs of asthmatic mice. Electroporation i.m. of the IL-19 gene into healthy mice up-regulated IL-4 and IL-5, but not IL-13. However, IL-19 up-regulated IL-13 in asthmatic mice. In vitro, IL-19 induced IL-4, IL-5, IL-10, and IL-13 production by activated T cells. Activation of T cells was required for induction of IL-13 because IL-19 did not induce IL-13 production on nonstimulated T cells. Taken together, these results demonstrated that IL-19 up-regulates Th2 cytokines on activated T cells and might play an important role in the pathogenesis of asthma.

Adult↗

PubMed2003

Cloning and characterization of mouse IL-22 binding protein.

Interleukin-22 (IL-22), a member of IL-10 family, plays some important roles in immune response through activation of the STAT 3 signal transduction pathway. Two types of IL-22-binding receptor have been discovered, a membrane-bound receptor and a soluble receptor, both encoded by different genes. IL-22 may be involved in inflammatory processes specifically regulated by soluble receptors. By screening a mouse genomic library for a human IL-22 binding protein homologue, we identified the mouse genomic clone of IL-22 binding protein. Its coding sequence was verified and isolated by RT-PCR. The gene encodes a protein of 230 amino acids that share 67.1% amino-acid sequence identity with human IL-22 binding protein. We designated this receptor 'mouse IL-22 binding protein' (mIL-22BP). mIL-22BP could be upregulated by LPS stimulation in mouse monocytes. mIL-22BP binds to mouse and human IL-22 and neutralizes STAT3 activation induced by both cytokines in human and rat hepatoma cell lines. Treating B cells with mouse IL-22 induces production of reactive oxygen species, which mIL-22BP blocks.

Amino Acid Sequence↗

PubMed2002

IL-19 induces production of IL-6 and TNF-alpha and results in cell apoptosis through TNF-alpha.

IL-10 is an immunosuppressive cytokine in the immune system. It was in clinical trial as an anti-inflammatory therapy for inflammatory bowel disease and various autoimmune diseases such as psoriasis, rheumatoid arthritis, and multiple sclerosis. IL-19 belongs to the IL-10 family, which includes IL-10, IL-19, IL-20, IL-22, melanoma differentiation-associated gene (MDA-7, IL-24), and AK155 (IL-26). Despite a partial homology in their amino acid sequences, they are dissimilar in their biologic functions. Little is known about the biologic function and gene regulation of IL-19. To understand the gene regulation of human IL-19, we identified a human IL-19 genomic clone and analyzed its promoter region. Five fusion genes containing different regions upstream of exon 1 linked to a luciferase reporter gene were expressed in the canine kidney epithelial-like Madin-Darby canine kidney cells. A fusion gene containing 394 bp showed luciferase activity 7- to 8-fold higher than the negative control of the promoterless fusion gene. We also isolated a full-length mouse cDNA clone. Mouse IL-19 shared 71% amino acid identity with human IL-19. Treatment of monocytes with mouse IL-19 induced the production of IL-6 and TNF-alpha. It also induced mouse monocyte apoptosis and the production of reactive oxygen species. Taken together, our results indicate that mouse IL-19 may play some important roles in inflammatory responses because it up-regulates IL-6 and TNF-alpha and induces apoptosis.

Amino Acid Sequence↗

PubMed2002

Regulatory effects of novel neurotrophin-1/b cell-stimulating factor-3 (cardiotrophin-like cytokine) on B cell function.

We describe regulatory effects that a novel neurotrophin-1/B cell-stimulating factor-3 (NNT-1/BSF-3; also reported as cardiotrophin-like cytokine) has on B cell function. NNT-1/BSF-3 stimulates B cell proliferation and Ig production in vitro. NNT-1/BSF-3-transgenic mice, engineered to express NNT-1/BSF-3 in the liver under control of the apolipoprotein E promoter, show B cell hyperplasia with particular expansion of the mature follicular B cell subset in the spleen and the prominent presence of plasma cells. NNT-1/BSF-3-transgenic mice show high serum levels of IgM, IgE, IgG2b, IgG3, anti-dsDNA Abs, and serum amyloid A. NNT-1/BSF-3-transgenic mice also show non-amyloid mesangial deposits that contain IgM, IgG, and C3 and are characterized by a distinctive ultrastructure similar to that of immunotactoid glomerulopathy. NNT-1/BSF-3-transgenic mice produce high amounts of Ag-specific IgM, IgA, and IgE and low amounts of IgG2a and IgG3. Normal mice treated with NNT-1/BSF-3 also produce high amounts of Ag-specific IgE. NNT-1/BSF-3 regulates immunity by stimulating B cell function and Ab production, with preference for Th2 over Th1 Ig types.

Animals↗