From Starfish Oocytes to Inflammation: The Unforeseeable Destiny of Roscovitine in Cystic Fibrosis

finity chromatography purification method combined with a simple kinase assay to search for potential pharmacological inhibitors, and this led to the discovery of roscovitine in Roscoff [4] . This molecule has been used extensively as a pharmacological tool to investigate the cell cycle, synchronize cells, and trigger cell cycle arrest or apoptosis, in order to evaluate its effects on numerous diseases ranging from cancers, viral infections, or neurodegeneration to polycystic kidney disease. While originally roscovitine was believed to exert its effects mainly on proliferating cells, Adriano Rossi and his colleagues (University of Edinburgh) reported that roscovitine also affected neutrophils, key cells in innate immunity deprived of proliferative capacities [5–10] . They discovered that roscovitine could trigger apoptosis of neutrophils, thereby favoring their phagocytosis by macrophages to promote the resolution of inflammation [11] . Notably, this activity was due to the inhibition of CDK7 and CDK9 involved in the regulation of RNA transcription [12] . These observations opened novel perspectives in the field of anti-inflammatory drugs and especially in chronic lung inflammation like that observed in CF patients. CF is indeed a complex genetic disease [13] that involves the mutation of the chloride channel CFTR gene, where the deletion of F508 is the most frequent mutation. Discoveries can take unpredictable paths! In a review presented in the current issue of the Journal of Innate Immunity , Meijer et al. [1] describe the rationale for evaluating roscovitine for the treatment of cystic fibrosis (CF) patients chronically infected with Pseudomonas aeruginosa . Roscovitine is a low-molecular-weight inhibitor of cyclin-dependent kinase (CDK) discovered over 20 years ago during studies on the regulation of cell division using a rather unlikely research subject, starfish oocytes [2] . Marine invertebrate oocytes and eggs have been used for decades to investigate cellular and molecular mechanisms involved in the regulation of the cell division cycle as these cells have a natural break at specific stages in the cell cycle [3] . In parallel to Xenopus oocytes and genetic models such as yeast and Drosophila , they have allowed the identification of the CDK1/cyclin B protein kinase as the major regulator in G2/M cell cycle transition. In fact, this discovery eventually led to the awarding of the Nobel Prize in Physiology or Medicine to Paul Nurse, Tim Hunt, and Leland H. Hartwell in 2001. CDK1/cyclin B is the archetype of CDKs that were found not only to be major players in all steps of the cell cycle but also to display other functions including a role in the central nervous system (CDK5/p25). Given that active CDK1/cyclin B is present in huge quantities in starfish M-phase oocytes, the group of Laurent Meijer at the CNRS (France) developed an afPublished online: April 26, 2016 Journal of Innate Immunity