PMID- 18650065
OWN - NLM
STAT- MEDLINE
DCOM- 20081216
LR  - 20171116
IS  - 0896-8411 (Print)
IS  - 0896-8411 (Linking)
VI  - 31
IP  - 2
DP  - 2008 Sep
TI  - The histone deacetylase inhibitor trichostatin A upregulates regulatory T cells 
      and modulates autoimmunity in NZB/W F1 mice.
PG  - 123-30
LID - 10.1016/j.jaut.2008.04.020 [doi]
AB  - We sought to determine if the histone deacetylase inhibitor (HDI), trichostatin A 
      (TSA), would alter systemic lupus erythematosus (SLE) in NZB/W mice. Fourteen to 
      sixteen-week-old female NZB/W F1 mice were given TSA (1.0mg/kg body weight (BW)) 
      intraperitonealy (i.p.) daily, TSA (1.0mg/kg BW) i.p.+anti-CD25 (250mg/mouse) 
      i.p. every third day, only anti-CD25 (250mg/mouse) i.p., DMSO or isotype IgG. 
      Disease progression was assessed as they aged. Mice were sacrificed at 26 or 38 
      weeks of age, tissues collected and evaluated. At 36 weeks, TSA-treated animals 
      had decreased anti-double stranded DNA (dsDNA) autoantibodies and decreased 
      protein excretion compared to controls. Spleen size and the percentage of 
      CD4+CD69+ cells were decreased, with an increase in CD4+CD25+ T cells in the 
      TSA-treated mice. Real-time reverse transcription-polymerase chain reaction 
      (RT-PCR) analysis of T cells showed a decrease in IL-6 production but an increase 
      in TGF-beta1 and Foxp3 in the TSA-treated animals. Kidney analysis showed a 
      decrease in IgG and C3 deposition, decrease in pathologic glomerular disease and 
      renal MCP-1, MMP-9, and IL-6 mRNA expression. Anti-CD25-treated mice euthanized 
      at 26 weeks of age showed decreased Foxp3+CD4+CD25+ T cells compared to 
      TSA-treated mice. These data suggest TSA administration modulates lupus-like 
      disease, in part, by increasing T regulatory cells.
FAU - Reilly, Christopher M
AU  - Reilly CM
AD  - Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional 
      College of Veterinary Medicine, Virginia Polytechnic Institute and State 
      University, VA, USA. chreilly@vcom.vt.edu
FAU - Thomas, Megan
AU  - Thomas M
FAU - Gogal, Robert Jr
AU  - Gogal R Jr
FAU - Olgun, Selen
AU  - Olgun S
FAU - Santo, Arben
AU  - Santo A
FAU - Sodhi, Renna
AU  - Sodhi R
FAU - Samy, Eileen T
AU  - Samy ET
FAU - Peng, Stanford L
AU  - Peng SL
FAU - Gilkeson, Gary S
AU  - Gilkeson GS
FAU - Mishra, Nilamadhab
AU  - Mishra N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080723
PL  - England
TA  - J Autoimmun
JT  - Journal of autoimmunity
JID - 8812164
RN  - 0 (Antibodies, Antinuclear)
RN  - 0 (CD4 Antigens)
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (Hydroxamic Acids)
RN  - 0 (Immunologic Factors)
RN  - 0 (Interleukin-2 Receptor alpha Subunit)
RN  - 3X2S926L3Z (trichostatin A)
SB  - IM
MH  - Animals
MH  - Antibodies, Antinuclear/blood
MH  - *Autoimmunity/drug effects
MH  - CD4 Antigens/metabolism
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - Female
MH  - Flow Cytometry
MH  - *Histone Deacetylase Inhibitors
MH  - Hydroxamic Acids/*pharmacology
MH  - Immunologic Factors/pharmacology
MH  - Interleukin-2 Receptor alpha Subunit/metabolism
MH  - Kidney/pathology
MH  - Lupus Erythematosus, Systemic/blood/drug therapy/*immunology
MH  - Mice
MH  - Mice, Inbred NZB
MH  - Organ Size
MH  - T-Lymphocytes, Regulatory/drug effects/*immunology
MH  - Up-Regulation/drug effects/immunology
EDAT- 2008/07/25 09:00
MHDA- 2008/12/17 09:00
CRDT- 2008/07/25 09:00
PHST- 2008/03/17 00:00 [received]
PHST- 2008/04/14 00:00 [revised]
PHST- 2008/04/15 00:00 [accepted]
PHST- 2008/07/25 09:00 [pubmed]
PHST- 2008/12/17 09:00 [medline]
PHST- 2008/07/25 09:00 [entrez]
AID - S0896-8411(08)00059-0 [pii]
AID - 10.1016/j.jaut.2008.04.020 [doi]
PST - ppublish
SO  - J Autoimmun. 2008 Sep;31(2):123-30. doi: 10.1016/j.jaut.2008.04.020. Epub 2008 
      Jul 23.