title: Modulation of granulocyte apoptosis can influence the resolution of inflammation.
abstract: Apoptosis of granulocytes and the subsequent clearance of apoptotic cells are important processes for the successful resolution of inflammation. Signalling pathways, including those involving NF-kappaB (nuclear factor kappaB), MAPK (mitogen-activated protein kinase) and PI3K (phosphoinositide 3-kinase) have been shown to be key regulators of inflammatory cell survival and apoptosis in vitro. In addition, manipulation of such pathways in vivo has indicated that they also play a role in the resolution of inflammation. Furthermore, manipulation of proteins directly involved in the control of apoptosis, such as Bcl-2 family members and caspases, can be targeted in vivo to influence inflammatory resolution. Recently, it has been shown that CDK (cyclin-dependent kinase) inhibitor drugs induce caspase-dependent human neutrophil apoptosis possibly by altering levels of the anti-apoptotic Bcl-2 family member, Mcl-1. Importantly, CDK inhibitor drugs augment the resolution of established 'neutrophil-dominant' inflammation by promoting apoptosis of neutrophils. Thus manipulation of apoptotic pathways, together with ensuring macrophage clearance of apoptotic cells, appears to be a viable pharmacological target for reducing established inflammation.
authors: MRC Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh Medical School, 47 Little France Crescent, Edinburgh, UK. a.g.rossi@ed.ac.uk
authors: A G
authors: AG
authors: Rossi
authors: J M
authors: JM
authors: Hallett
authors: D A
authors: DA
authors: Sawatzky
authors: M M
authors: MM
authors: Teixeira
authors: C
authors: C
authors: Haslett
mesh_terms: D017209:Apoptosis; D006098:Granulocytes / Q000166:cytology* / Q000502:physiology*; D006706:Homeostasis; D006801:Humans; D007249:Inflammation / Q000503:physiopathology* / Q000517:prevention & control*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000502:physiology; D015398:Signal Transduction
chemical_list: D016328:NF-kappa B; D020928:Mitogen-Activated Protein Kinases