Jump to content

Toll-like receptor 4: Difference between revisions

From Wikipedia, the free encyclopedia
Browse history interactively
← Previous editNext edit →
Content deleted Content added
VisualWikitext
Line 22: Line 22:
* [[Levorphanol]]<ref name="pmid19679181"/>
* [[Levorphanol]]<ref name="pmid19679181"/>
* [[Pethidine]]<ref name="pmid19679181"/>
* [[Pethidine]]<ref name="pmid19679181"/>
* [[Glucuronoxylomannan]]<ref name="pmid16299344"/>
* Glucuronoxylomannan from [[Cryptococcus]]<ref name="pmid16299344"/>
* [[Fentanyl]]<ref name="pmid19679181"/>
* [[Fentanyl]]<ref name="pmid19679181"/>
* [[Methadone]]<ref name="pmid19679181"/>
* [[Methadone]]<ref name="pmid19679181"/>

Revision as of 01:29, 31 August 2012

Template:PBB Toll-like receptor 4 is a protein that in humans is encoded by the TLR4 gene.[1][2] TLR 4 is a toll-like receptor. It detects lipopolysaccharide from Gram-negative bacteria and is thus important in the activation of the innate immune system. TLR 4 has also been designated as CD284 (cluster of differentiation 284).

The protein encoded by this gene is a member of the Toll-like receptor (TLR) family, which plays a fundamental role in pathogen recognition and activation of innate immunity. TLRs are highly conserved from Drosophila to humans and share structural and functional similarities. They recognize pathogen-associated molecular patterns (PAMPs) that are expressed on infectious agents, and mediate the production of cytokines necessary for the development of effective immunity. The various TLRs exhibit different patterns of expression. This receptor is most abundantly expressed in placenta, and in myelomonocytic subpopulation of the leukocytes. It has been implicated in signal transduction events induced by lipopolysaccharide (LPS) found in most gram-negative bacteria. Mutations in this gene have been associated with differences in LPS responsiveness. Also, several transcript variants of this gene have been found, but the protein-coding potential of most of them is uncertain.[3]

Signaling pathway of toll-like receptors. Dashed grey lines represent unknown associations

Interactions

TLR 4 has been shown to interact with TOLLIP,[4] Myd88[5][6][7][8] and Lymphocyte antigen 96.[9][10] Researchers from NTNU have described how intracellular trafficking of TLR4 is dependent on the GTPase Rab-11a, and knock down of Rab-11a results in hampered TLR4 recruitment to E. coli-containing phagosomes and subsequent reduced signal transduction through the MyD88-independent pathway[11] . A recent study [1] has suggested a link between the TLR 4 receptor and binge drinking; when researchers manipulated the genes responsible for the expression of TLR 4 and GABA receptors in rodents that had been bred and trained to drink excessively, the animals showed a "profound reduction" in drinking behaviours. Additionally, it has been shown that ethanol, even in the absence of LPS, can activate TLR4 signaling pathways.[12]

Toll-like receptor 4 has also been shown to be important for the long-term side-effects of opioid analgesic drugs. Various μ-opioid receptor ligands have been tested and found to also possess action as agonists or antagonists of TLR4, with opioid agonists such as morphine being TLR4 agonists, while opioid antagonists such as naloxone were found to be TLR4 antagonists. Activation of TLR4 leads to downstream release of inflammatory modulators including TNF-α and Interleukin-1, and constant low-level release of these modulators is thought to reduce the efficacy of opioid drug treatment with time, and be involved in both the development of tolerance to opioid analgesic drugs,[13][14] and in the emergence of side-effects such as hyperalgesia and allodynia that can become a problem following extended use of opioid drugs.[15][16] Drugs that block the action of TNF-α or IL-1β have been shown to increase the analgesic effects of opioids and reduce the development of tolerance and other side-effects,[17][18] and this has also been demonstrated with drugs that block TLR4 itself. Interestingly the response of TLR4 to opioid drugs has been found to be enantiomer-independent, so the "unnatural" enantiomers of opioid drugs such as morphine and naloxone, which lack affinity for opioid receptors, still produce the same activity at TLR4 as their "normal" enantiomers.[19][20] This means that the unnatural enantiomers of opioid antagonists, such as (+)-naloxone, can be used to block the TLR4 activity of opioid analgesic drugs, while leaving the μ-opioid receptor mediated analgesic activity unaffected.[21])[20][22] This may also be the mechanism behind the beneficial effect of ultra-low dose naltrexone on opioid analgesia.[23]

Drugs targeting TLR4

Agonists

Antagonists

References

  1. ^ Rock FL, Hardiman G, Timans JC, Kastelein RA, Bazan JF (1998). "A family of human receptors structurally related to Drosophila Toll". Proc Natl Acad Sci U S A. 95 (2): 588–93. doi:10.1073/pnas.95.2.588. PMC 18464. PMID 9435236. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  2. ^ Medzhitov R, Preston-Hurlburt P, Janeway CA Jr (1997). "A human homologue of the Drosophila Toll protein signals activation of adaptive immunity". Nature. 388 (6640): 394–7. doi:10.1038/41131. PMID 9237759. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  3. ^ "Entrez Gene: TLR 4 toll-like receptor 4".
  4. ^ Zhang, Guolong (2002). "Negative regulation of toll-like receptor-mediated signaling by Tollip". J. Biol. Chem. 277 (9). United States: 7059–65. doi:10.1074/jbc.M109537200. ISSN 0021-9258. PMID 11751856. {{cite journal}}: Cite has empty unknown parameters: |laydate=, |laysummary=, and |laysource= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)CS1 maint: unflagged free DOI (link)
  5. ^ Chuang, Tsung-Hsien (2004). "Triad3A, an E3 ubiquitin-protein ligase regulating Toll-like receptors". Nat. Immunol. 5 (5). United States: 495–502. doi:10.1038/ni1066. ISSN 1529-2908. PMID 15107846. {{cite journal}}: Cite has empty unknown parameters: |laydate=, |laysummary=, and |laysource= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  6. ^ Doyle, Sean E (2003). "Toll-like receptor 3 mediates a more potent antiviral response than Toll-like receptor 4". J. Immunol. 170 (7). United States: 3565–71. ISSN 0022-1767. PMID 12646618. {{cite journal}}: Cite has empty unknown parameters: |laydate=, |laysummary=, and |laysource= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  7. ^ Rhee, S H (2000). "Murine TOLL-like receptor 4 confers lipopolysaccharide responsiveness as determined by activation of NF kappa B and expression of the inducible cyclooxygenase". J. Biol. Chem. 275 (44). UNITED STATES: 34035–40. doi:10.1074/jbc.M007386200. ISSN 0021-9258. PMID 10952994. {{cite journal}}: Cite has empty unknown parameters: |laydate=, |laysummary=, and |laysource= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)CS1 maint: unflagged free DOI (link)
  8. ^ Fitzgerald, K A (2001). "Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction". Nature. 413 (6851). England: 78–83. doi:10.1038/35092578. ISSN 0028-0836. PMID 11544529. {{cite journal}}: Cite has empty unknown parameters: |laydate=, |laysummary=, and |laysource= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  9. ^ Re, Fabio (2002). "Monomeric recombinant MD-2 binds toll-like receptor 4 tightly and confers lipopolysaccharide responsiveness". J. Biol. Chem. 277 (26). United States: 23427–32. doi:10.1074/jbc.M202554200. ISSN 0021-9258. PMID 11976338. {{cite journal}}: Cite has empty unknown parameters: |laydate=, |laysummary=, and |laysource= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)CS1 maint: unflagged free DOI (link)
  10. ^ Shimazu, R (1999). "MD-2, a Molecule that Confers Lipopolysaccharide Responsiveness on Toll-like Receptor 4". J. Exp. Med. 189 (11). UNITED STATES: 1777–82. doi:10.1084/jem.189.11.1777. ISSN 0022-1007. PMC 2193086. PMID 10359581. {{cite journal}}: Cite has empty unknown parameters: |laydate=, |laysummary=, and |laysource= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  11. ^ Espevik T, Husebye H, Aune MH, Stenvik J (2010). "The Rab11a GTPase controls Toll-like receptor 4-induced activation of interferon regulatory factor-3 on phagosomes". Immunity. 33 (4): 583–596. doi:10.1016/j.immuni.2010.09.010. PMID 20933442. {{cite journal}}: Cite has empty unknown parameters: |laydate=, |laysummary=, and |laysource= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  12. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 16272348, please use {{cite journal}} with |pmid=16272348 instead.
  13. ^ Shavit Y, Wolf G, Goshen I, Livshits D, Yirmiya R (2005). "Interleukin-1 antagonizes morphine analgesia and underlies morphine tolerance". Pain. 115 (1–2): 50–9. doi:10.1016/j.pain.2005.02.003. PMID 15836969. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  14. ^ Mohan S, Davis RL, DeSilva U, Stevens CW (2010). "Dual regulation of mu opioid receptors in SK-N-SH neuroblastoma cells by morphine and interleukin-1β: evidence for opioid-immune crosstalk". Journal of Neuroimmunology. 227 (1–2): 26–34. doi:10.1016/j.jneuroim.2010.06.007. PMC 2942958. PMID 20615556. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  15. ^ Komatsu T, Sakurada S, Katsuyama S, Sanai K, Sakurada T (2009). "Mechanism of allodynia evoked by intrathecal morphine-3-glucuronide in mice". International Review of Neurobiology. International Review of Neurobiology. 85: 207–19. doi:10.1016/S0074-7742(09)85016-2. ISBN 978-0-12-374893-5. PMID 19607972.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  16. ^ a b Lewis SS, Hutchinson MR, Rezvani N, Loram LC, Zhang Y, Maier SF, Rice KC, Watkins LR (2010). "Evidence that intrathecal morphine-3-glucuronide may cause pain enhancement via toll-like receptor 4/MD-2 and interleukin-1β". Neuroscience. 165 (2): 569–83. doi:10.1016/j.neuroscience.2009.10.011. PMC 2795035. PMID 19833175. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  17. ^ Shen CH; Tsai RY; Shih MS; et al. (2011). "Etanercept restores the antinociceptive effect of morphine and suppresses spinal neuroinflammation in morphine-tolerant rats". Anesth. Analg. 112 (2): 454–9. doi:10.1213/ANE.0b013e3182025b15. PMID 21081778. {{cite journal}}: Unknown parameter |author-separator= ignored (help); Unknown parameter |month= ignored (help)
  18. ^ Hook MA; Washburn SN; Moreno G; et al. (2011). "AN IL-1 RECEPTOR ANTAGONIST BLOCKS A MORPHINE-INDUCED ATTENUATION OF LOCOMOTOR RECOVERY AFTER SPINAL CORD INJURY". Brain, Behavior, and Immunity. 25 (2): 349–59. doi:10.1016/j.bbi.2010.10.018. PMC 3025088. PMID 20974246. {{cite journal}}: Unknown parameter |author-separator= ignored (help); Unknown parameter |month= ignored (help)
  19. ^ a b Watkins LR, Hutchinson MR, Rice KC, Maier SF (2009). "The "Toll" of Opioid-Induced Glial Activation: Improving the Clinical Efficacy of Opioids by Targeting Glia". Trends in Pharmacological Sciences. 30 (11): 581–91. doi:10.1016/j.tips.2009.08.002. PMC 2783351. PMID 19762094. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  20. ^ a b c Hutchinson MR, Zhang Y, Brown K, Coats BD, Shridhar M, Sholar PW, Patel SJ, Crysdale NY, Harrison JA, Maier SF, Rice KC, Watkins LR (2008). "Non-stereoselective reversal of neuropathic pain by naloxone and naltrexone: involvement of toll-like receptor 4 (TLR4)". The European Journal of Neuroscience. 28 (1): 20–9. doi:10.1111/j.1460-9568.2008.06321.x. PMC 2588470. PMID 18662331. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  21. ^ Hutchinson MR, Coats BD, Lewis SS, Zhang Y, Sprunger DB, Rezvani N, Baker EM, Jekich BM, Wieseler JL, Somogyi AA, Martin D, Poole S, Judd CM, Maier SF, Watkins LR (2008). "Proinflammatory cytokines oppose opioid induced acute and chronic analgesia". Brain, Behavior, and Immunity. 22 (8): 1178–89. doi:10.1016/j.bbi.2008.05.004. PMC 2783238. PMID 18599265. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  22. ^ Hutchinson MR, Lewis SS, Coats BD, Rezvani N, Zhang Y, Wieseler JL, Somogyi AA, Yin H, Maier SF, Rice KC, Watkins LR (2010). "Possible involvement of Toll-Like Receptor 4/MD-2 activity of opioid inactive isomers causes spinal proinflammation and related behavioral consequences". Neuroscience. 167 (3): 880–93. doi:10.1016/j.neuroscience.2010.02.011. PMC 2854318. PMID 20178837. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  23. ^ Lin SL, Tsai RY, Tai YH, Cherng CH, Wu CT, Yeh CC, Wong CS (2010). "Ultra-low dose naloxone upregulates interleukin-10 expression and suppresses neuroinflammation in morphine-tolerant rat spinal cords". Behavioural Brain Research. 207 (1): 30–6. doi:10.1016/j.bbr.2009.09.034. PMID 19799935. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  24. ^ a b c d e f g h i j k l Hutchinson MR, Zhang Y, Shridhar M; et al. (2010). "Evidence that opioids may have toll-like receptor 4 and MD-2 effects". Brain Behav. Immun. 24 (1): 83–95. doi:10.1016/j.bbi.2009.08.004. PMC 2788078. PMID 19679181. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link) Cite error: The named reference "pmid19679181" was defined multiple times with different content (see the help page).
  25. ^ Cite error: The named reference pmid16299344 was invoked but never defined (see the help page).
  26. ^ Wu HE, Hong JS, Tseng LF (2007). "Stereoselective action of (+)-morphine over (−)-morphine in attenuating the (−)-morphine-produced antinociception via the naloxone-sensitive sigma receptor in the mouse". European Journal of Pharmacology. 571 (2–3): 145–51. doi:10.1016/j.ejphar.2007.06.012. PMC 2080825. PMID 17617400. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  27. ^ Kelley KW, Dantzer R (2011). "Alcoholism and inflammation: neuroimmunology of behavioral and mood disorders". Brain Behav. Immun. 25 Suppl 1: S13–20. doi:10.1016/j.bbi.2010.12.013. PMID 21193024. {{cite journal}}: Unknown parameter |month= ignored (help)
  28. ^ a b c d e f g Hutchinson MR, Loram LC, Zhang Y, Shridhar M, Rezvani N, Berkelhammer D, Phipps S, Foster PS, Landgraf K, Falke JJ, Rice KC, Maier SF, Yin H, Watkins LR (2010). "Evidence that tricyclic small molecules may possess Toll-like receptor and MD-2 activity". Neuroscience. 168 (2): 551–63. doi:10.1016/j.neuroscience.2010.03.067. PMC 2872682. PMID 20381591. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link) Cite error: The named reference "pmid20381591" was defined multiple times with different content (see the help page).
  29. ^ Tidswell, M; Tillis, W; Larosa, SP; Lynn, M; Wittek, AE; Kao, R; Wheeler, J; Gogate, J; Opal, SM (2010). "Phase 2 trial of eritoran tetrasodium (E5564), a Toll-like receptor 4 antagonist, in patients with severe sepsis". Critical Care Medicine. 38 (1): 72–83. doi:10.1097/CCM.0b013e3181b07b78. PMID 19661804.

Further reading

Template:PBB Further reading

Template:PBB Controls

Retrieved from "https://en.wikipedia.org/w/index.php?title=Toll-like_receptor_4&oldid=510038753"