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"Alternative Medicine" Article "Alternativ medicin" artikel
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TLR4 - cluster of differentiation 284 TLR4 - klynge af differentiering 284

By Expert Author: Stephen Jones Ved ekspert Forfatter: Stephen Jones
View Summary | Submitted: 2008-07-11 | Word Count: 659 words | Views: 130 view(s) Vis Resumé | Forelagt: 2008-07-11 | Ordoptælling: 659 ord | Views: 130 se (s)
Stephen Jones
Toll-like receptor 4 (TLR4) often designated as CD284 (cluster of differentiation 284) is a class I transmembrane receptor belonging to the large homologous family of Toll like receptors. Toll-lignende receptor 4 (TLR4) ofte udpeget som CD284 (klynge af differentiering 284) er en klasse I transmembrane receptor tilhører det store homologt familie af Toll gerne receptorer. TLR4 expressed on the surface of immune system cells, is activated by exposure to lipopolysaccharides derived from the outer membrane of Gram negative bacteria and thus forms part of the innate immune response in mammals. TLR4 udtrykt på overfladen af immunsystemet celler, der aktiveres ved eksponering for lipopolysaccharides stammer fra den ydre membran af Gram-negative bakterier og dermed udgør en del af den medfødte immunrespons hos pattedyr. (1) TLR4 was initially cloned as the human homolog of Drosophila Toll (dToll) and thus was first named hToll. (1) TLR4 var oprindeligt klonede som det humane homolog af Drosophila Toll (dToll) og dermed først blev navngivet hToll. Like all other members of the TLR family, TLR4 is composed of an extracellular domain containing multiple leucine-rich repeats (LRRs), a transmembrane region, and a cytoplasmic tail containing the conserved TIR domain. Som alle andre medlemmer af TLR familie, TLR4 er sammensat af en ekstracellulære domæne indeholder flere leucin-rige gentager (LRRs), en transmembrane region, og en cytoplasmic hale indeholder de bevares TIR domæne. TLR4 maps to chromosome 9q32-33. TLR4 kort til kromosom 9q32-33. It shows a high degree of similarity to dToll over the entire aminoacid sequence. Det viser en høj grad af lighed til dToll hele medhjælper sekvens. The TLR4 sequence encodes an 839 aminoacid protein with 22 N-terminal LRR regions and a calculated molecular weight of 90 kDa. Den TLR4 sekvens koder en 839 medhjælper protein med 22 N-terminal LRR regioner og en beregnet molekylevægt på 90 kDa. TLR4 is most closely related to TLR1 and TLR6 each with 25% overall aa sequence identity. TLR4 er meget tæt forbundet med TLR1 og TLR6 hver med 25% samlet aa sekvens identitet. Several transcript variants of this gene have been found, but the protein coding potential of most of them is uncertain. Flere afskrift varianter af dette gen er fundet, men det protein kodende potentiale i de fleste af dem er usikker.

In vivo, TLR4 mRNA is expressed as a single transcript, and found at highest levels in spleen and PBLs. In vivo, TLR4 mRNA er udtrykt i en enkelt afskrift, og findes på højeste niveau i milt og PBLs. (2, 3) Of the PBL populations, TLR4 is expressed by B cells, DCs, monocytes, macrophages, granulocytes, and T cells. (2, 3) Af de PBL populationer, TLR4 er udtrykt af B-celler, DCS, monocytter, makrofager, granulocytter, og T-celler. Other reports suggest that TLR4 is only expressed in myelomonocytic cells and is highest in mononuclear cells. Andre rapporter tyder på, at TLR4 er kun udtrykt i myelomonocytic celler og er højest i mononukleære celler. In vitro, TLR4 mRNA and protein expression is upregulated in THP-1 cells upon PMA-induced differentiation. In vitro, TLR4 mRNA og protein udtryk er upregulated i THP-1 celler på PMA-induceret differentiering. TLR4 is moderately upregulated by autocrine IFN-γ, IL-1β. TLR4 er moderat upregulated ved autocrine IFN-γ, IL-1β. TLR4 mRNA expression in THP-1 cells is unaffected by exposure to both Gram-positive and Gram-negative bacteria. TLR4 mRNA udtryk i THP-1 celler er upåvirket af eksponering for både Gram-positive og Gram-negative bakterier. Ex vivo, granulocyte, and especially monocyte, TLR4 expression is upregulated upon exposure to Gram-negative bacteria. Ex vivo, granulocyt, og især monocyt, TLR4 udtryk er upregulated, når den udsættes for Gram-negative bakterier. (4)

TLR4 is critical for host defense against gram-negative bacteria in both mice and humans. TLR4 er kritisk for værten forsvar mod gram-negative bakterier i både mus og mennesker. Upon recognition of its ligand LPS, TLR4 undergoes dimerization, and recent studies suggest that this causes concerted conformational changes in the receptor leading to self association of the cytoplasmic Toll/Interleukin 1 receptor (TIR) signalling domain. Efter anerkendelsen af dens ligand LPS, TLR4 gennemgår dimerization, og de seneste undersøgelser tyder på, at dette skaber samordnet conformational ændringer i receptoren fører til selvstændig sammenslutning af cytoplasmic Toll / interleukin 1 receptor (TIR) signalering domæne. Ligand recognition by TLR4 requires the extracellular association of an additional component, MD-2 which together can initiate two major intracellular signaling pathways, MyD88-dependent and TRIF-dependent (MyD88-independent). Ligand anerkendelse af TLR4 kræver det ekstracellulære sammenslutning af en ekstra komponent, MD-2, som tilsammen kan indlede to store intracellulære signalveje der, MyD88-afhængige og TRIF-afhængige (MyD88-uafhængige). The MyD88-dependent pathway requires the recruitment of TIRAP and MyD88 via homophilic TIR-TIR interactions and activates nuclear factor (NF)-κB, activator protein-1 (AP-1) and interferon regulatory factor 5 (IRF5), which induce inflammatory cytokine expression such as IL-6, IL-12, and TNFα. Den MyD88 afhængige pathway kræver ansættelse af TIRAP og MyD88 via homophilic TIR-TIR interaktioner og aktiverer nuklear faktor (NF)-κB, aktivator protein-1 (AP-1) og interferon regulerende faktor 5 (IRF5), som inducerer inflammatoriske cytokin udtryk såsom IL-6, IL-12, og TNFa. The TRIF-dependent pathway requires the recruitment of TRAM and TRIF and activates IRF3, in addition to NF-κB and AP-1, which induce type I interferon (IFN) expression. Den TRIF-afhængige pathway kræver ansættelse af sporvogne og TRIF og aktiverer IRF3 som supplement til NF-κB og AP-1, som inducerer type I interferon (IFN) udtryk. TLR4 can also activate various other signaling molecules, including phosphatidylinositol-3 kinase (PI-3K) and MAP3Ks such as MEKK3, TPL2, and ASK1. TLR4 kan også aktivere forskellige andre signaling molekyler, herunder phosphatidylinositol-3 kinase (PI-3K) og MAP3Ks såsom MEKK3, TPL2, og ASK1. (5,6) The TLR4 complex also recognizes a few other bacterial PAMPs including LTA. (5,6) Den TLR4 komplekse også genkender nogle få andre bakterielle PAMPs herunder LTA. Further, the TLR4 complex recognizes viruses including respiratory syncytial virus (RSV), hepatitis C virus (HCV), and mouse mammary tumor virus (MMTV). Endvidere er den TLR4 komplekse genkender virus herunder respiratorisk syncytialvirus virus (RSV), hepatitis C virus (HCV), og musen brystkirtler tumor virus (MMTV). The TLR4 complex can also recognize endogenous ligands, for example, heat shock proteins, fibrinogen, fibronectin, surfactant protein A (SP-A), and β-defensins. Den TLR4 kompleks kan også genkende ligander, for eksempel, varme shock proteiner, fibrinogen, fibronectin, surfactant protein A (SP-A), og β-defensins. TLR4 also forms heterodimers both with TLR5, which presumably enhances its activity, and also with TLR1, which inhibits its activity. TLR4 også former heterodimers både med TLR5, hvilket formentlig øger sin aktivitet, og også med TLR1, som hæmmer dens aktivitet. (7, 8) (7, 8)

Mutations in TLR4 gene have been associated with differences in LPS responsiveness. Mutationer i TLR4 gen har været forbundet med forskelle i LPS lydhørhed.
A recently discovered Asp299Gly TLR4 polymorphism has been identified that confer differences in the inflammatory response elicited by bacterial lipopolysaccharide and is associated with a decreased risk of atherosclerosis. En nylig opdaget Asp299Gly TLR4 polymorfisme er blevet identificeret, at give forskelle i inflammatorisk reaktion fremkaldes ved bakterielle lipopolysaccharide og er forbundet med en nedsat risiko for aterosklerose. (9)

Reference:
1. Ricardo et al. Ricardo et al. PLoS ONE. PLoS ONE. 2007; 2(8): e788. 2007; 2 (8): e788.
2. Medzhitov, R. et al. Medzhitov, R. et al. (1997) Nature 388:394. (1997) Nature 388:394.
3. Rock, FL et al. Rock, FL et al. (1998) Proc. (1998) Proc. Natl. Acad. Sci. USA 95:588. USA 95:588.
4. Zarember, KA and PJ Godowski (2002) J. Immunol. Zarember, KA og PJ Godowski (2002) J. Immunol. 168:554.
5. Myeong Sup Lee Vol. Myeong sup Lee vol. 76: 447-480 Annual Review of Biochemistry 76: 447-480 Annual Review of Biochemistry
6. Yong-Chen Lu doi:10.1016/j.cyto.2008.01.006 Article in press Yong-Chen Lu DOI: 10.1016/j.cyto.2008.01.006 artikel i pressen
7. Spitzer, JH et al. Spitzer, JH et al. (2002) Eur. (2002) Eur. J. Immunol. J. Immunol. 32:1182.
8. Mizel, SB et al. Mizel, SB et al. (2003) J. Immunol. (2003) J. Immunol. 170:6217.
9. N Engl J Med 2002; 347:1978-1980, Dec 12, 2002. N Engl J Med 2002; 347:1978-1980, 12 december 2002.
About the Author/Author Bio Om Forfatter / Author Bio

IMGENEX India Pvt Ltd. the only biotech company in Orissa and one of its kinds in Eastern India. IMGENEX India Pvt Ltd den eneste biotekvirksomhed i Orissa og en af sin slags i det østlige Indien. IMGENEX India started in Oct as an outsourcing branch of IMGENEX Corporation , San Diego, USA. IMGENEX Indien begyndte i oktober som en outsourcing filial af IMGENEX Corporation, San Diego, USA. Find out more information about Toll-like receptors . Få mere information om Toll-lignende receptorer.

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Looking for neti pot salt. Leder du efter neti pot salt. Here's a handy guide for you to help you understand what kinds of neti pot salt is available and how to determine which one is right for you. Her er en praktisk guide for dig og hjælpe dig med at forstå, hvilke former for neti pot salt er til rådighed, og hvordan du kan afgøre, hvilken en der er rigtigt for dig. Neti Pot salt is available commercially as prepackaged individual mixes and also it can be found in bulk form. Neti Pot salt findes i handelen som færdigpakkede individuelle blandinger og også det kan findes i løs form. The bulk neti pot salt is usually found in containers or even plastic bags. Hovedparten neti pot salt er normalt findes i containere eller plastposer. Neti salt comes in a variety of strengths or saline concentrations. Neti salt kommer i forskellige styrker og saltholdigt koncentrationer.
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