Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The kinetics of gene expression associated with the development of cutaneous graft-versus-host disease (GVHD) were examined in a mouse model of MHC-matched allogeneic hematopoietic stem cell transplantation. Ear skin was obtained from recipient mice with or without GVHD between 7 and 40 days after transplantation for histopathological analysis and gene expression profiling. Gene expression patterns were consistent with early infiltration and activation of CD8(+) T and mast cells, followed by CD4(+) T, natural killer, and myeloid cells. The sequential infiltration and activation of effector cells correlated with the histopathological development of cutaneous GVHD and was accompanied by up-regulated expression of many chemokines and their receptors (CXCL-1, -2, -9, and -10; CCL-2, -5, -6, -7, -8, -9, -11, and -19; CCR-1 and CCR-5), adhesion molecules (ICAM-1, CD18, Ly69, PSGL-1, VCAM-1), molecules involved in antigen processing and presentation (TAP1 and TAP2, MHC class I and II, CD80), regulators of apoptosis (granzyme B, caspase 7, Bak1, Bax, and BclII), interferon-inducible genes (STAT1, IRF-1, IIGP, GTPI, IGTP, Ifi202A), stimulators of fibroblast proliferation and matrix synthesis (interleukin-1beta, transforming growth factor-beta1), and markers of keratinocyte proliferation (keratins 5 and 6), and differentiation (small proline-rich proteins 2E and 1B). Many acute-phase proteins were up-regulated early in murine cutaneous GVHD including serum amyloid A2 (SAA2), SAA3, serpins a3g and a3n, secretory leukocyte protease inhibitor, and metallothioneins 1 and 2. The kinetics of gene expression were consistent with the evolution of cutaneous pathology as well as with current models of disease progression during cutaneous GVHD.
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PMID:Kinetics of gene expression in murine cutaneous graft-versus-host disease. 1516 52

The aim of this study was to investigate the relationship between the plasma levels of chemokine CCL-2/MCP-1 and acute graft-versus-host disease (aGVHD) and/or idiopathic pneumonia syndrome (IPS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). ELISA assays were used to detect the plasma level of CCL-2/MCP-1 of 22 patients who received allo-HSCT, including 14 patients without or with grade I, 8 patients with grade II - IV aGVHD, respectively. 8 out of 22 patients were also diagnosed with IPS clinically. The dynamic changes of the plasma levels of CCL-2/MCP-1 chemokine and its correlation with aGVHD and/or IPS were analysized retrospectively. The results showed that the plasma levels of CCL-2/MCP-1 in the patients with moderate and serious aGVHD (grade II - IV) significantly increased, as compared with that prior to allo-HSCT (p < 0.05). The plasma levels of CCL-2/MCP-1 in the patients with aGVHD and/or IPS were higher significantly than those without any of these complications (p = 0.001). The retrospective analysis indicated that the plasma levels of CCL-2/MCP-1 in the patients with IPS significantly increased (p = 0.006). It is concluded that plasma level of CCL-2/MCP-1 correlates with aGVHD and/or IPS, and plays a role in the pathogenesis of these complications.
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PMID:[Correlation of chemokine CCL-2/MCP-1 level in the plasma with aGVHD and idiophathic pneumonia syndrome after allogeneic hematopoietic stem cell transplantation]. 1871 72

The chemokine family consists of approximately 50 small (8-14 kDa), basic proteins that are expressed and released by a wide range of normal and malignant cells. Most chemokines act through heptahelical transmembrane G protein- coupled receptors. Based on their molecular structure these cytokines are divided into the two major subgroups CCL and CXCL chemokines that bind to CCR or CXCR receptors respectively. Primary human acute myelogenous leukemia (AML) cells show constitutive release of a wide range of chemokines, but the chemokine release profile differs between patients. Among the commonly expressed chemokines are proangiogenic CXCL8, antiangiogenic CXCL4/9-11 and several leukocyte-chemotactic chemokines. Systemic serum levels of leukocyte-chemotactic chemokines depend both on patient age, disease status, the chemotherapy regimen and development of complicating infections. The local chemokine network in human AML is probably further modulated by the hypoxic bone marrow microenvironment and the local release of chemokines by nonleukemic bone marrow stromal cells. Usually primary AML cells also express several chemokine receptors. Specific chemokine inhibitors are now being developed, including chemokine-neutralizing or receptor-blocking antibodies, antisense strategies, receptor-blocking small molecules or inhibitors of downstream signaling. The use of CXCR4-antagonists for mobilization of peripheral blood stem cells has been documented in several clinical studies. Although animal studies suggest that chemokine inhibition also may become useful in the treatment of graft versus host disease, the possible use of chemokine-targeting therapy for other indications than stem cell mobilization requires further studies.
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PMID:The chemokine system and its contribution to leukemogenesis and treatment responsiveness in patients with acute myeloid leukemia. 1978 55