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: 8USQdkYkHre,g7h_ ,{N~ ,{ N~ ,{V~ ,{N~    N:$e2$e2 @wE : x*, --  N:$e2$e2 @)"wE  : z*, --  N :$e2$e2 @&2wE : z*, --H  0ZIޚ ? 3380___PPT10.  ؞!jgX 0 PX(  ~  s *Xzu+16% u ~  s *Hu*(/-F: u :  3 A5F  Bwu? ?"6?@`NNN?N 3y= " Innate immune responses to microbial ligands: The role of Toll-like receptors TLRs(W)Y6qMQuS^Sag-Nv\O(u bJTNProf. Dr. Artur J. Ulmer Head of the Division of Cellular Immunology, Reserch Center Borstel, Borstel, Germany bJTe2012t^5g7e NHS 9:30~11:30 bJT0WpYm;SNb OguʋlV[͑p[[6A-19 O[ Q[XdThe innate immune system constitutes the first most important defense barrier against invading pathogens. One prominent receptor family, which is involved in the recognition of invading microbes in mamalia, is the evolutionarily ancient Toll-like receptor (TLR) family. The cytoplasmatic and signaling domain of TLRs is evolutionarily homolog to the cytoplamatic domain of Toll of the Drosophila fly. So far 10 different TLRs have been described in human, each recognizing a distinct molecular pattern within their ligands (so called pathogen-associated molecular patterns, PAMPs). TLR4 was the first TLR, which has been discovered to be activated by a microbial ligand, namely lipopolysaccharide (LPS) from the outer cell wall of Gram-negative bacteria. TLR2 is unique to form heteromers with TLR1 or TLR2. It is the common view that triacylated bacterial lipopeptides (LP) sense TLR1/2 heteromers, whereas diacylated bacterial LP are recognized by TLR6/2 heteromers. A third prominent TLR is the TLR9, recognizing CpG-rich unmethylated DNA fragments.6ccf<!.  )      E         "     ;    Z    4    T         R     /                      '     1           **  H  0ZIޚ ? 3380___PPT10. 0  (  x  c $:+16% : x  c $:*(/-F: : :  3 A5F  6s' 3? >MSP-RON Pathway in Innate Immunity and Inflammation: Therapeutic Potential and Molecular Mechanism MSP-RON_(W)Y6qMQuTpu-Nv\O(u \o(WvluSvQRP[:g6R bJTNsfwm OguʋlV[͑p[[_lf[yrXYec Amarillo Community Endowed Chair in Cancer Research, Director of School of Pharmacy Cancer Biology Center, Texas Tech University Health Sciences Center School of Pharmacy, Amarillo, Texas, USA bJTe2012t^5g7e NHS 2:00~4:00 bJT0WpYm;SNb6B-14y iu:S:yYe[ Q[XdHyperactive inflammation in various infectious diseases attributes to dysregulated innate immune response, which ultimately leads to tissue damage and organ failure. Uncontrolled activation of toll-like receptors (TLRs) in tissue macrophages is the major cause for the pathological events. Through genetic, biochemical, and biological studies, macrophages-stimulating protein (MSP) and its receptor tyrosine kinase RON were identified as potent endogenous regulators that inhibit inflammatory reactions during bacterial infection and T-cell mediated immune responses. Such anti-inflammatory activities are manifested by RON-mediated signaling that impairs TLR-4-NF-B signaling events. Specifically, MSP activates cellular protein SHP that inhibits inflammatory mediator production and to minimizing inflammatory reactions. To develop biotherapeutics that boost RON signaling, monoclonal antibodies (mAb) specific to RON were produced and characterized. These mAbs are agonistic in vitro, which potently stimulate RON and downstream signaling molecules by tissue macrophages and suppress iNOS/Cox-2 production by inflammatory macrophages. In vivo animal studies further revealed that RON-agonistic mAbs are highly effective in protecting mice against LPS-induced septic death. Thus, our findings uncover powerful endogenous inhibitors of inflammation. Moreover, the generation of RON-agonistic mAbs provides a novel platform for controlling inflammation occurred during infection and immune disorderBf6! ,l<  **  H  0ZIޚ ? 3380___PPT10.r@?]# 61Oh+'0p `h|   õƬ 1 ΢û ΢û16Microsoft Office PowerPoint@֒@&@$x')Ghg  ,V'&" WMFCɢ <8?@ABCDEFGHIJKLMNOPQRSTUVWXYZ[\]^_`abcdefghijklmnopqrstuvwxyz{|}~      !"#$%&'()*+,-./0123456789:;<=>?@ABCDEFGHIJKLMNOPQRSTUVWXYZ[\]^_`abcdefghijklmnopqrstuvwxyz{|}~      !"#$%&'()*+,-./0123456789:;<=>?@ABCDEFGHIJKLMNOPQRSTUVWXYZ[\]^_`abcdfghijklnopqrst{Root EntrydO)PicturesCurrent UsermSummaryInformation(PowerPoint Document(6DocumentSummaryInformation8e