By Tracey J. Mitchell, Timothy J. Williams (auth.), Dr. L. Gordon Letts, Dr. Douglas W. Morgan (eds.)
In November 1998 a few of the key leaders of latest drug discovery for inflammatory ailments amassed at Hershey, Pennsylvania for the ninth foreign convention of the irritation examine organization. The convention was once held over a 5 day interval and supplied a stimulating atmosphere for the open alternate of significant advances in simple irritation examine in addition to new drug discovery and improvement. This ebook encompasses many of the highlights of a number of displays made on the convention. It comprises many of the most up-to-date and significant advancements within the box of irritation study. subject matters comprise the prestige of eotaxin and chemokines in bronchial asthma and hypersensitivity, sign transduction and law of various mediators resembling the JNK crew of MAP kinases, TNF and IL-1 signaling of NF-kB in addition to regulators of AP-1, macrophage metalloproteinases, lymphotoxin and extra insights into the position of MCP-1 in ailment. additionally mentioned are drug pursuits in rheumatoid and osteoarthritis, fibrotic diseases,...
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Additional info for Inflammatory Processes:: Molecular Mechanisms and Therapeutic Opportunities
SP100030 represents a new class of Tcell-specific dual inhibitors of NF-KB and AP-1 mediated inflammatory gene expression, and suggests that cell-specific inhibitors of inflammatory gene expression can indeed be identified. An interesting implication, possibly related to the cross-regulation of NF-KB and AP-1 activity by MAP kinase pathways, is that T cells possess a common target protein that controls the functions of both NF-KB and AP-l. Future prospects Because AP-1 and NF-KB are regulated by cascades of intracellular enzymes, including kinases and ubiquitin ligases, much of the current drug discovery efforts are 48 Small molecule regulators of Ap·1 and NF-KB focused on identifying specific inhibitors of these enzymes.
API proteins bind to DNA and activate transcription as Jun homodimers, Jun-Jun heterodimers, or Jun-Fos heterodimers. There are multiple Jun and Fos family members (c-Jun, JunB, JunO and c-Fos, FosB, Fra-l, Fra-2) which are expressed in different cell types and mediate the transcription of both unique and overlapping genes. API is also a component of the nuclear factor of activated T cells (NFAT) complex responsible for the transcription of the IL-2 gene and other cytokine genes in activated T cells  .
Cell 90: 373-383 Ling L, Cao Z, Goeddel DV (1998) NF-KB-inducing kinase activates IKK-a by phosphorylation of Ser-176. Proc Natl Acad Sci USA 95: 3792-3797 Nakano H, Shindo M, Sakon S, Nishinaka S, Mihara M, Yagita H, Okumura K (1998) Differential regulation of IKE kinase a and b by two upstream kinases, NF-KB-inducing kinase and mitogen-activated protein kinaselERK kinase kinase-I. Proc Natl Acad Sci USA 95: 3537-3542 Lee FS, Peters RT, Dang LC, Maniatis T (1998) MEKK1 activates both IKB kinase a and [3.
Inflammatory Processes:: Molecular Mechanisms and Therapeutic Opportunities by Tracey J. Mitchell, Timothy J. Williams (auth.), Dr. L. Gordon Letts, Dr. Douglas W. Morgan (eds.)