By Alberto Mantovani, Paola Allavena, Silvano Sozzani (auth.), Prof. Dr. Eckhard Kownatzki, Dr. Johannes Norgauer (eds.)
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It used to be just lately that many physicians and biomedical scientists felt that the period of 'vaccines' for shielding mankind opposed to infectious affliction used to be coming to an finish. in the course of the 1 940s and 50s the common use of newly constructed antibiotics and antimicrobial chemotherapeutic brokers advised a brand new period in drugs, i.
"One may still quite pass horne and mesh a internet than bounce into the pond and dive some distance fishes" (Chinese proverb) spotting the proper analytical query and making plans the research in accordance ly is unquestionably the 1st prerequisite for winning hint and ultratrace determina tions. the second one prerequisite is to choose the tactic acceptable to the analyti cal specification.
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A proximal sequence 127 to 51 bp upstream of the transcription start site of the murine MIP-1~ gene is bound by members of the ATF/CREB family of transcription factors and serves as an LPS-responsive element . The RANTES promoter region contains four NF-lCB sites essentially involved in gene regulation, of which the two distant ones (position -213, and -579 relative to the transcription start site) overlap with an NF-AT binding site and a CD28-responsive element, respectively . The two tandemly arranged KB-like sequences in close proximity of the transcription start site bind not only to Rei family members but also to late expressed non-Rei factors (responsive region: -71 to -53) upregulated 3 to 5 days following activation .
This sequence is conserved in the neutrophil-stimulating members of the chemokine family and is a prerequisite for the binding of MGSA and NAP-2 to CXCR2. Peptides containing the Glu-Leu-Arg sequence were, however, not capable of binding to or activating the IL-8 receptors, and a mutant of IL-8 in which the Glu-Leu-Arg sequence was replaced with alanines could still activate both the CXCR1 and CXCR2, when added in high concentrations. In lower concentrations these mutant CXC chemokines, especially those in which the Glu-Leu-Arg sequence was replaced with Ala-Ala-Arg, became antagonists [7, 8].
J BioI Chern 269: 19343-19348 21 Hayashi S, Kurdowska A, Miller EJ, Albright ME, Girten BE, Cohen AB (1995) Synthetic hexa- and heptapeptides which inhibit IL-8 from binding to and activating human blood neutrophils. J Irnrnuno/154: 814-824 22 Wu L, Ruffing N, Shi X, Newman W, Soler D, Mackay CR, Qin S (1996) Discrete steps in binding and signaling of interleukin-8 with its receptor. J Bioi Chern 271: 3120231207 23 Monteclaro FS, Charo IF (1996) The amino-terminal extracellular domain of the MCP1 receptor, but not the RANTES/MIP-la receptor, confers chemokine selectivity.