Novel pharmacological strategies for driving inflammatory cell apoptosis and enhancing the resolution of inflammation.
Resolution of inflammation requires the effective downregulation of key inflammatory cells such as neutrophils and eosinophils, which normally undergo programmed cell death (apoptosis) to enable their detection and removal by phagocytes such as macrophages. Dysregulation of this process is thought to contribute to the pathogenesis and progression of chronic inflammatory disorders such as chronic obstructive pulmonary disease, asthma, rheumatoid arthritis, allergic rhinitis and inflammatory bowel disease. Importantly, knowledge of the signalling pathways responsible for the induction and execution of granulocyte apoptosis and the phagocytic removal of apoptotic cells continues to increase and, with it, the potential for incisive pharmacological intervention. In this article, we highlight pharmacological strategies that could be used to drive the resolution of inflammation by augmenting apoptosis of inflammatory cells.
Hallett
John M
JM
MRC Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh Medical School, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
Leitch
Andrew E
AE
Riley
Nicola A
NA
Duffin
Rodger
R
Haslett
Christopher
C
Rossi
Adriano G
AG
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D006098:Granulocytes / Q000276:immunology / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000502:physiology; D010587:Phagocytosis / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D019869:Phosphatidylinositol 3-Kinases; D018844:Cyclin-Dependent Kinases