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Dysregulated Expression (dysregulated + expression)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Lymphotoxin and LIGHT signaling pathways and target genes

IMMUNOLOGICAL REVIEWS, Issue 1 2004
Kirsten Schneider
Summary:, Lymphotoxins (LT, and LT,), LIGHT [homologous to LT, inducible expression, competes with herpes simplex virus (HSV) glycoprotein D for HSV entry mediator (HVEM), a receptor expressed on T lymphocytes], tumor necrosis factor (TNF), and their specific receptors LT,R, HVEM, and TNF receptor 1 (TNFR1) and TNFR2, form the immediate family of the larger TNF superfamily. These cytokines establish a critical communication system required for the development of secondary lymphoid tissues; however, knowledge of the target genes activated by these signaling pathways is limited. Target genes regulated by the LT,,-LT,R pathway include the tissue-organizing chemokines, CXCL13, CCL19, and CCL21, which establish cytokine circuits that regulate LT expression on lymphocytes, leading to organized lymphoid tissue. Infectious disease models have revealed that LT,, pathways are also important for innate and adaptive immune responses involved in host defense. Here, regulation of interferon-, by LT,R and TNFR signaling may play a crucial role in certain viral infections. Regulation of autoimmune regulator in the thymus via LT,R implicates LT/LIGHT involvement in central tolerance. Dysregulated expression of LIGHT overrides peripheral tolerance leading to T-cell-driven autoimmune disease. Blockade of TNF/LT/LIGHT pathways as an intervention in controlling autoimmune diseases is attractive, but such therapy may have risks. Thus, identifying and understanding the target genes may offer an opportunity to fine-tune inhibitory interventions. [source]

Dysregulated expression of bcl-2 and bax in oral carcinomas: evidence of post-transcriptional control

JOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 2 2000
Yu Chen
Abstract: A study was conducted to investigate the gene expression of bcl-2 and bax in oral squamous cell carcinomas. We used reverse,transcriptase-polymerase chain reacion (RT,PCR) to evaluate the expression of bcl-2 and bax mRNAs and the ratio of bcl-2/bax mRNA, and employed immunohistochemistry to investigate the bcl-2- and bax- encoded proteins. It was observed that the expression level of bcl-2 mRNA or bax mRNA was not consistent with their protein level in some cases. Higher expression of bcl-2 mRNA and stronger immunostaining of bcl-2 protein were found in oral squamous cell carcinomas than in the adjacent histologically normal oral epithelium. These findings were more prominent in poorly differentiated carcinomas. No significant differences in bax mRNA and protein were observed between carcinomas and the adjacent histologically normal oral epithelium. However, poorly differentiated carcinomas showed very weak immunostaining for bax. The ratio of bcl-2/bax mRNA was higher in carcinomas than in the adjacent histologically normal oral epithelium, and higher ratios were seen in most of poorly differentiated carcinomas. This study supplies indirect evidence of post-transcriptional control of bcl-2 and bax expression, and suggests that dysregulated expression of bcl-2 and bax may be related to the differentiation of oral squamous cell carcinomas. [source]

Involvement of leptin signaling in the survival and maturation of bone marrow-derived dendritic cells

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2006
Kwan Lam, Queenie
Abstract Previous studies demonstrated that lymphocyte development is impaired in leptin receptor (Ob - R)-deficient db/db mice. However, it remains unclear whether or not leptin signaling plays a physiological role in dendritic cell (DC) development and function. In this study, we first detected Ob-R expression in murine DC. Using db/db mice at a pre-diabetic stage, we demonstrate that the total number of DC generated from bone marrow (BM) cultures is significantly lower than in WT controls. Similarly, selective blockade of leptin with a soluble mouse Ob-R chimera (Ob-R:Fc) inhibited DC generation in wild-type BM cultures. The reduced DC yield in db/db BM culture was attributed to significantly increased apoptosis, which was associated with dysregulated expression of Bcl-2 family genes. Moreover, db/db DC displayed markedly reduced expression of co-stimulatory molecules and a Th2-type cytokine profile, with a poor capacity to stimulate allogeneic T cell proliferation. Consistent with their impaired DC phenotype and function, db/db DC showed significantly down-regulated activities of the PI3K/Akt pathway as well as STAT-3 and I,B-,. In conclusion, our findings demonstrate the involvement of leptin signaling in DC survival and maturation. See accompanying commentary: http://dx.doi.org/10.1002/eji.200636770 [source]

Prolonged expression of CD154 on CD4 T cells from pediatric lupus patients correlates with increased CD154 transcription, increased nuclear factor of activated T cell activity, and glomerulonephritis

ARTHRITIS & RHEUMATISM, Issue 8 2010
Jay Mehta
Objective To assess CD154 expression in patients with pediatric systemic lupus erythematosus (SLE) and to explore a transcriptional mechanism that may explain dysregulated expression of CD154. Methods Cell surface CD154 expression (pre- and postactivation) in peripheral blood CD4 T cells from 29 children with lupus and 29 controls matched for age, sex, and ethnicity was examined by flow cytometry. CD154 expression was correlated with clinical features, laboratory parameters, and treatments received. Increased CD154 expression on CD4 T cells from the SLE patients was correlated with CD154 message and transcription rates by real-time reverse transcription,polymerase chain reaction (RT-PCR) and nuclear run-on assays, respectively. Nuclear factor of activated T cell (NF-AT) transcription activity and mRNA levels in CD4 T cells from SLE patients were explored by reporter gene analysis and real-time RT-PCR, respectively. Results CD154 surface protein levels were increased 1.44-fold in CD4 T cells from SLE patients as compared with controls in cells evaluated 1 day postactivation ex vivo. This increase correlated clinically with the presence of nephritis and an elevated erythrocyte sedimentation rate. Increased CD154 protein levels also correlated with increased CD154 mRNA levels and with CD154 transcription rates, particularly at later time points following T cell activation. Reporter gene analyses revealed a trend for increased NF-AT, but decreased activator protein 1 and similar NF-,B, activity in CD4 T cells from SLE patients as compared with controls. Moreover, NF-AT1 and, in particular, NF-AT2 mRNA levels were notably increased in CD4 T cells from SLE patients as compared with controls. Conclusion Following activation, cell surface CD154 is increased on CD4 T cells from pediatric lupus patients as compared with controls, and this increase correlates with the presence of nephritis, increased CD154 transcription rates, and increased NF-AT activity. These results suggest that NF-AT/calcineurin inhibitors, such as tacrolimus and cyclosporine, may be beneficial in the treatment of lupus nephritis. [source]