Cyclin-dependent kinase inhibitors enhance the resolution of inflammation by promoting inflammatory cell apoptosis - PubMed (original) (raw)
. 2006 Sep;12(9):1056-64.
doi: 10.1038/nm1468. Epub 2006 Sep 3.
Deborah A Sawatzky, Annemieke Walker, Carol Ward, Tara A Sheldrake, Nicola A Riley, Alison Caldicott, Magdalena Martinez-Losa, Trevor R Walker, Rodger Duffin, Mohini Gray, Elvira Crescenzi, Morag C Martin, Hugh J Brady, John S Savill, Ian Dransfield, Christopher Haslett
Affiliations
- PMID: 16951685
- DOI: 10.1038/nm1468
Cyclin-dependent kinase inhibitors enhance the resolution of inflammation by promoting inflammatory cell apoptosis
Adriano G Rossi et al. Nat Med. 2006 Sep.
Erratum in
- Nat Med. 2006 Dec;12(12):1434. Dosage error in article text
Abstract
Apoptosis is essential for clearance of potentially injurious inflammatory cells and subsequent efficient resolution of inflammation. Here we report that human neutrophils contain functionally active cyclin-dependent kinases (CDKs), and that structurally diverse CDK inhibitors induce caspase-dependent apoptosis and override powerful anti-apoptosis signals from survival factors such as granulocyte-macrophage colony-stimulating factor (GM-CSF). We show that the CDK inhibitor R-roscovitine (Seliciclib or CYC202) markedly enhances resolution of established neutrophil-dependent inflammation in carrageenan-elicited acute pleurisy, bleomycin-induced lung injury, and passively induced arthritis in mice. In the pleurisy model, the caspase inhibitor zVAD-fmk prevents R-roscovitine-enhanced resolution of inflammation, indicating that this CDK inhibitor augments inflammatory cell apoptosis. We also provide evidence that R-roscovitine promotes apoptosis by reducing concentrations of the anti-apoptotic protein Mcl-1. Thus, CDK inhibitors enhance the resolution of established inflammation by promoting apoptosis of inflammatory cells, thereby demonstrating a hitherto unrecognized potential for the treatment of inflammatory disorders.
Similar articles
- The cyclin-dependent kinase inhibitor R-roscovitine down-regulates Mcl-1 to override pro-inflammatory signalling and drive neutrophil apoptosis.
Leitch AE, Riley NA, Sheldrake TA, Festa M, Fox S, Duffin R, Haslett C, Rossi AG. Leitch AE, et al. Eur J Immunol. 2010 Apr;40(4):1127-38. doi: 10.1002/eji.200939664. Eur J Immunol. 2010. PMID: 20127676 - Effects of the cyclin-dependent kinase inhibitor R-roscovitine on eosinophil survival and clearance.
Farahi N, Uller L, Juss JK, Langton AJ, Cowburn AS, Gibson A, Foster MR, Farrow SN, Marco-Casanova P, Sobolewski A, Condliffe AM, Chilvers ER. Farahi N, et al. Clin Exp Allergy. 2011 May;41(5):673-87. doi: 10.1111/j.1365-2222.2010.03680.x. Epub 2011 Jan 24. Clin Exp Allergy. 2011. PMID: 21255143 - Seliciclib (CYC202 or R-roscovitine), a small-molecule cyclin-dependent kinase inhibitor, mediates activity via down-regulation of Mcl-1 in multiple myeloma.
Raje N, Kumar S, Hideshima T, Roccaro A, Ishitsuka K, Yasui H, Shiraishi N, Chauhan D, Munshi NC, Green SR, Anderson KC. Raje N, et al. Blood. 2005 Aug 1;106(3):1042-7. doi: 10.1182/blood-2005-01-0320. Epub 2005 Apr 12. Blood. 2005. PMID: 15827128 Free PMC article. - Cyclin-dependent kinase inhibitor drugs as potential novel anti-inflammatory and pro-resolution agents.
Leitch AE, Haslett C, Rossi AG. Leitch AE, et al. Br J Pharmacol. 2009 Oct;158(4):1004-16. doi: 10.1111/j.1476-5381.2009.00402.x. Epub 2009 Sep 23. Br J Pharmacol. 2009. PMID: 19775281 Free PMC article. Review. - Role of neutrophil apoptosis in the resolution of inflammation.
El Kebir D, Filep JG. El Kebir D, et al. ScientificWorldJournal. 2010 Sep 1;10:1731-48. doi: 10.1100/tsw.2010.169. ScientificWorldJournal. 2010. PMID: 20842319 Free PMC article. Review.
Cited by
- RNA kinetics influence the response to transcriptional perturbation in leukaemia cell lines.
Todorovski I, Tsang MJ, Feran B, Fan Z, Gadipally S, Yoannidis D, Kong IY, Bjelosevic S, Rivera S, Voulgaris O, Zethoven M, Hawkins ED, Simpson KJ, Arnau GM, Papenfuss AT, Johnstone RW, Vervoort SJ. Todorovski I, et al. NAR Cancer. 2024 Oct 3;6(4):zcae039. doi: 10.1093/narcan/zcae039. eCollection 2024 Dec. NAR Cancer. 2024. PMID: 39372038 Free PMC article. - Spatiotemporal control of neutrophil fate to tune inflammation and repair for myocardial infarction therapy.
Kim C, Kim H, Sim WS, Jung M, Hong J, Moon S, Park JH, Kim JJ, Kang M, Kwon S, Kim MJ, Ban K, Park HJ, Kim BS. Kim C, et al. Nat Commun. 2024 Oct 1;15(1):8481. doi: 10.1038/s41467-024-52812-6. Nat Commun. 2024. PMID: 39353987 Free PMC article. - Metabolic changes in fibroblast-like synoviocytes in rheumatoid arthritis: state of the art review.
Hu Z, Li Y, Zhang L, Jiang Y, Long C, Yang Q, Yang M. Hu Z, et al. Front Immunol. 2024 Feb 28;15:1250884. doi: 10.3389/fimmu.2024.1250884. eCollection 2024. Front Immunol. 2024. PMID: 38482018 Free PMC article. Review. - Neutrophils facilitate the epicardial regenerative response after zebrafish heart injury.
Peterson EA, Sun J, Chen X, Wang J. Peterson EA, et al. Dev Biol. 2024 Apr;508:93-106. doi: 10.1016/j.ydbio.2024.01.011. Epub 2024 Jan 28. Dev Biol. 2024. PMID: 38286185 - Beyond host defense and tissue injury: the emerging role of neutrophils in tissue repair.
Rizo-Téllez SA, Filep JG. Rizo-Téllez SA, et al. Am J Physiol Cell Physiol. 2024 Mar 1;326(3):C661-C683. doi: 10.1152/ajpcell.00652.2023. Epub 2024 Jan 8. Am J Physiol Cell Physiol. 2024. PMID: 38189129 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources