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

We previously discovered a hamster monoclonal antibody, TAB4, against mouse PSGL-1/CD162 that can induce death of activated T cells. Here, we further investigated the potential of TAB4 in treating two murine models of T cell-mediated diseases. The results showed that administration of TAB4 suppressed incidence and severity of both GVHD and type I diabetes. Analyses of apoptotic T cells ex vivo shortly after antibody injection revealed a higher percentage of apoptosis among activated T cells in the TAB4-treated group than in the control group. Furthermore, restoration of functional donor T cells was observed in TAB4-treated mice. As TAB4 does not affect the binding of P-selectin to activated T cells, our data suggest that its long-lasting therapeutic effect on inhibiting disease progression is attained by specifically inducing apoptosis of activated T cells. These data hence extend our previous finding of the novel property of PSGL-1 and strongly indicate that the PSGL-1-specific apoptosis-inducing antibody is a new therapeutic agent possessing a great potential for controlling GVHD and other T cell-mediated autoimmune diseases.
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PMID:A novel apoptosis-inducing anti-PSGL-1 antibody for T cell-mediated diseases. 1594 16