Targeting innate immunity protein kinase signalling in inflammation.
Inflammation is an evolutionarily conserved host reaction that is initiated in response to trauma, tissue damage and infection. It leads to changes in tissue homeostasis and blood flow, immune-cell activation and migration, and secretion of cytokines and mediators in a spatio-temporally coordinated manner. Progress in understanding of the mechanisms of the inflammatory response has identified various protein kinases that act as essential signalling components and therefore represent potential therapeutic targets. This article summarizes advances in the identification and validation of such targets, and discusses key issues for the development of small-molecule kinase inhibitors as a new generation of oral anti-inflammatory drugs, including feedback loops, inhibitor specificity and combination therapy.
Gaestel
Matthias
M
Hannover Medical School, Institute of Biochemistry, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. gaestel.matthias@mh-hannover.de
Kotlyarov
Alexey
A
Kracht
Michael
M
D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods* / Q000639:trends; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D007249:Inflammation / Q000188:drug therapy / Q000201:enzymology / Q000276:immunology; D018836:Inflammation Mediators / Q000008:administration & dosage* / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use*; D011494:Protein Kinases / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology
D018836:Inflammation Mediators; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases