HDAC inhibitors: modulating leukocyte differentiation, survival, proliferation and inflammation.
Therapeutic effects of histone deacetylase (HDAC) inhibitors in cancer models were first linked to their ability to cause growth arrest and apoptosis of tumor cells. It is now clear that these agents also have pleiotropic effects on angiogenesis and the immune system, and some of these properties are likely to contribute to their anti-cancer activities. It is also emerging that inhibitors of specific HDACs affect the differentiation, survival and/or proliferation of distinct immune cell populations. This is true for innate immune cells such as macrophages, as well as cells of the acquired immune system, for example, T-regulatory cells. These effects may contribute to therapeutic profiles in some autoimmune and chronic inflammatory disease models. Here, we review our current understanding of how classical HDACs (HDACs 1-11) and their inhibitors impact on differentiation, survival and proliferation of distinct leukocyte populations, as well as the likely relevance of these effects to autoimmune and inflammatory disease processes. The ability of HDAC inhibitors to modulate leukocyte survival may have implications for the rationale of developing selective inhibitors as anti-inflammatory drugs.
The University of Queensland, Institute for Molecular Bioscience and Australian Infectious Diseases Research Centre, Brisbane, Queensland, Australia. m.sweet@imb.uq.edu.au
Matthew J
MJ
Sweet
Melanie R
MR
Shakespear
Nabilah A
NA
Kamal
David P
DP
Fairlie
D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000517:prevention & control; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D056572:Histone Deacetylase Inhibitors; D007527:Isoenzymes; D006655:Histone Deacetylases