Kinetics of gene expression in murine cutaneous graft-versus-host disease.
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.
Sugerman
Philip B
PB
straZeneca Research and Development Boston, Waltham, Massachusetts, USA.
Faber
Sara B
SB
Willis
Lucy M
LM
Petrovic
Aleksandra
A
Murphy
George F
GF
Pappo
Jacques
J
Silberstein
David
D
van den Brink
Marcel R M
MR
D000818:Animals; D018925:Chemokines / Q000235:genetics; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics*; D006086:Graft vs Host Disease / Q000235:genetics* / Q000473:pathology; D007700:Kinetics; D008285:Major Histocompatibility Complex; D051379:Mice; D019707:Receptors, Chemokine / Q000235:genetics; D012867:Skin / Q000473:pathology*; D033581:Stem Cell Transplantation / Q000009:adverse effects
D018925:Chemokines; D019707:Receptors, Chemokine