Kinetics of gene expression in murine cutaneous graft-versus-host disease Journal Article
| Authors: | Sugerman, P. B.; Faber, S. B.; Willis, L. M.; Petrovic, A.; Murphy, G. F.; Pappo, J.; Silberstein, D.; van den Brink, M. R. M. |
| Article Title: | Kinetics of gene expression in murine cutaneous graft-versus-host disease |
| Abstract: | 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-1β, transforming growth factor-β1), 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. |
| Keywords: | controlled study; unclassified drug; disease course; histopathology; nonhuman; t lymphocyte; animal cell; mouse; animals; mice; animal tissue; protein bcl 2; stat1 protein; unindexed drug; gene expression; gene expression profiling; interleukin 1beta; vascular cell adhesion molecule 1; stem cell transplantation; skin; gene expression regulation; granzyme b; chemokine; kinetics; nucleotide sequence; serine proteinase inhibitor; major histocompatibility antigen class 2; graft versus host reaction; transforming growth factor beta1; allogeneic hematopoietic stem cell transplantation; natural killer cell; effector cell; bone marrow cell; enzyme-linked immunosorbent assay; lymphocytic infiltration; disease models, animal; major histocompatibility complex; graft vs host disease; intercellular adhesion molecule 1; t lymphocyte activation; chemokines; chemokine receptor; receptors, chemokine; b7 antigen; cell adhesion molecule; major histocompatibility antigen class 1; keratin; protein bax; mast cell; protein bak; caspase 7; chemokine receptor ccr5; alpha chemokine; chemokine receptor ccr1; serum amyloid a; cd18 antigen; metallothionein i; interferon regulatory factor 1; priority journal; article; keratin 5; keratin 6; protein bak1; secretory leukocyte proteinase inhibitor |
| Journal Title: | American Journal of Pathology |
| Volume: | 164 |
| Issue: | 6 |
| ISSN: | 0002-9440 |
| Publisher: | Elsevier Science, Inc. |
| Date Published: | 2004-06-01 |
| Start Page: | 2189 |
| End Page: | 2202 |
| Language: | English |
| PROVIDER: | scopus |
| PMCID: | PMC1615752 |
| PUBMED: | 15161652 |
| DOI: | 10.1016/S0002-9440(10)63776-5 |
| DOI/URL: | |
| Notes: | Am. J. Pathol. -- Cited By (since 1996):43 -- Export Date: 16 June 2014 -- Source: Scopus |
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