Molecular therapeutic targets in inflammation: cyclooxygenase and NF-kappaB.
Inflammation is the host response to infection and injury. Inflammatory cells respond to foreign substances and inflammatory stimulus by producing bioactive mediators such as prostanoids, cytokines and chemokines. These mediators have complex, pleiotropic effects and interact with many cell types to amplify the inflammatory response. Dysregulation of these processes can lead to acute and chronic inflammatory diseases and pharmacological intervention is necessary to attenuate cellular inflammation pathways. Cyclooxygenase-2, the key inducible enzyme responsible for producing prostanoids, and the nuclear factor-kappa B (NF-kappaB) activation pathway, which regulates the transcription of inflammatory genes, represent attractive targets for developing anti-inflammatory therapeutics, as both pathways are activated by diverse inflammatory stimuli. This article reviews recent advances in anti-inflammatory drug development in both of these areas. Selective inhibitors of inflammation including cyclooxygenase inhibitors, antibodies against inflammatory cytokines, cytokine receptor antagonist, antibodies against adhesion molecules and therapeutics directed against the NF-kappaB activation pathway will be discussed.
Krakauer
Teresa
T
Department of Molecular Biology and Immunology, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702-5011, USA. Teresa.Krakauer@det.amedd.army.mil
D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015815:Cell Adhesion Molecules / Q000276:immunology; D002986:Clinical Trials as Topic; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D016207:Cytokines / Q000037:antagonists & inhibitors; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D007375:Interleukin-1 / Q000037:antagonists & inhibitors; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008565:Membrane Proteins; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; D007375:Interleukin-1; D007527:Isoenzymes; D008565:Membrane Proteins; D016328:NF-kappa B; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C466421:cyclooxygenase-3