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Details for receptor: TLR4

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EndoNet ID: ENR00843

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Synonyms

  • toll-like receptor 4
  • TLR4
  • hToll
  • human toll protein
  • CD284 antigen

General information

  • Highly expressed in placenta, spleen and peripheral blood leukocytes. Detected in monocytes, macrophages, dendritic cells and several types of T-cells. [1]
  • Exposure to bacterial products, such as LPS or lipoarabinomannan, or to proinflammatory cytokines increased TLR4 expression in monocytes and polymorphonuclear leukocytes, whereas IL-10 blocked this effect. [2]
  • Epithelial cells derived from normal human vagina, ectocervix, and endocervix failed to express TLR4 as well as MD2, two essential components of the receptor complex for LPS in phagocytes and endothelial cells. [3]
  • IL-1RI and TLR4 are expressed on bronchial epithelial cells. The functional TLR4 complex requires the glycoprotein CD14 and the helper molecule MD-2 for optimal signaling. [4]
  • TLR-4 expression on peripheral blood monocytes did not significantly differ between the control and cirrhotic groups. [5]
  • Cooperates with LY96 and CD14 to mediate the innate immune response to bacterial lipopolysaccharide (LPS). Acts via MyD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. [1]
  • TLR4 and the accessory molecule MD-2 are constitutively expressed in distinct human alveolar and bronchial epithelial cells. [6]
  • Human oviductal stromal fibroblasts, but not oviductal epithelial cells, express Toll-like receptor 4. [7]
  • Human dermal microvessel endothelial cells (HMEC) and human umbilical vein endothelial cells express predominantly TLR-4 but very weak TLR-2. [8]

Links to other resources

UniProt O00206
Ensembl ENST00000394487

Subunit information

Sequence 
ESWEPCVEV VPNITYQCM ELNFYKIPD 
NLPFSTKNL DLSFNPLRH LGSYSFFSF 
PELQVLDLS RCEIQTIED GAYQSLSHL 
STLILTGNP IQSLALGAF SGLSSLQKL 
VAVETNLAS LENFPIGHL KTLKELNVA 
HNLIQSFKL PEYFSNLTN LEHLDLSSN 
KIQSIYCTD LRVLHQMPL LNLSLDLSL 
NPMNFIQPG AFKEIRLHK LTLRNNFDS 
LNVMKTCIQ GLAGLEVHR LVLGEFRNE 
GNLEKFDKS ALEGLCNLT IEEFRLAYL 
DYYLDDIID LFNCLTNVS SFSLVSVTI 
ERVKDFSYN FGWQHLELV NCKFGQFPT 
LKLKSLKRL TFTSNKGGN AFSEVDLPS 
LEFLDLSRN GLSFKGCCS QSDFGTTSL 
KYLDLSFNG VITMSSNFL GLEQLEHLD 
FQHSNLKQM SEFSVFLSL RNLIYLDIS 
HTHTRVAFN GIFNGLSSL EVLKMAGNS 
FQENFLPDI FTELRNLTF LDLSQCQLE 
QLSPTAFNS LSSLQVLNM SHNNFFSLD 
TFPYKCLNS LQVLDYSLN HIMTSKKQE 
LQHFPSSLA FLNLTQNDF ACTCEHQSF 
LQWIKDQRQ LLVEVERME CATPSDKQG 
MPVLSLNIT CQMNKTIIG VSVLSVLVV 
SVVAVLVYK FYFHLMLLA GCIKYGRGE 
NIYDAFVIY SSQDEDWVR NELVKNLEE 
GVPPFQLCL HYRDFIPGV AIAANIIHE 
GFHKSRKVI VVVSQHFIQ SRWCIFEYE 
IAQTWQFLS SRAGIIFIV LQKVEKTLL 
RQQVELYRL LSRNTYLEW EDSVLGRHI 
FWRRLRKAL LDGKSWNPE GTVGTGCNW 
QEATSI

Binding hormones

    Anatomical structures with this receptor

    • placenta

    • spleen

    • leukocyte

    • monocyte

    • dendritic_cell_in_lymphoid_tissues

      Influences

      • positive IFN-beta
        • TLR4 can lead to IFN-beta production. [9]

    • macrophage

      Influences

      • positive IFN-beta
        • With LPS in the presence of LPS-binding protein TLR4 activates the common MyD88-dependent signaling pathway as well as a MyD88-independent pathway leading to interferon-beta production. [10]
      • positive IFN-alpha
      • positive IL-1 beta
        • IL-1β is first synthesized as biologically-inactive precursor (pro-IL-1β) in response to Toll-like receptor (TLR) agonists in macrophages. [11]

    • lipocyte_of_liver

      Induced phenotypes

      • regulation of innate immune response
        • TLR4-stimulated HSCs produce various chemokines and express adhesion molecules to recruit Kupffer cells and/or circulating macrophages by the site of HSCs. [12]
        • The activation of TLR4 signaling enhances TGF-β signaling, that downregulates the expression of BMP and activin membrane bound inhibitor (Bambi) for firogenic response. [13]
      • Activated human HSCs express TLR4 and its coreceptors MD-2 and CD14. [14]

    • Kupffer_cell_stellate_cell_of_liver

      Influences

      • positive IL-8
        • LPS directly acts through TLR4 and then activates NF-kappa B and JNK to induce proinflammatory chemokines and adhesion molecules in activated human HSCs. [14]
      • positive TNF-alpha
        • LPS activates Kupffer cells to produce mediators such as TNF-alpha. [14]
      • positive IL-18
        • LPS induces IL-18 secretion from Kupffer cells in a caspase-1-dependent manner. [15]

    • peripheral blood mononuclear cell (PBMC)

    • neutrophil_granulocyte

    • lung

    • continuous_vascular_endothelial_cell_of_blood_vessels_and_lymphatics

    • epithelial_cell_with_microvilli

    • epithelial_cell

    • stromal_fibroblast

      Influences

      • positive GCP-2

    • cholangiocyte

    • bronchial_epithelial_cell

      Influences

      • positive IL-8

    • B-lymphocyte

    • pneumocyte_type_II

    Reference