Toll-like receptor 5

Last updated
TLR5
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases TLR5 , MELIOS, SLE1, SLEB1, TIL3, toll like receptor 5
External IDs OMIM: 603031 MGI: 1858171 HomoloGene: 20698 GeneCards: TLR5
Orthologs
SpeciesHumanMouse
Entrez

7100

53791

Ensembl

ENSG00000187554

ENSMUSG00000079164

UniProt

O60602

Q9JLF7

RefSeq (mRNA)

NM_003268

NM_016928

RefSeq (protein)

NP_003259

NP_058624

Location (UCSC) Chr 1: 223.11 – 223.14 Mb Chr 1: 182.78 – 182.8 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Toll-like receptor 5, also known as TLR5, is a protein which in humans is encoded by the TLR5 gene. [5] It is a member of the toll-like receptor (TLR) family. TLR5 is known to recognize bacterial flagellin from invading mobile bacteria. [6] It has been shown to be involved in the onset of many diseases, which includes Inflammatory bowel disease. [7] Recent studies have also shown that malfunctioning of TLR5 is likely related to rheumatoid arthritis, [8] [9] osteoclastogenesis, and bone loss. [10] Abnormal TLR5 functioning is related to the onset of gastric, cervical, endometrial and ovarian cancers. [11] [12]

Contents

Function

The TLR family 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. TLR5 is expressed on both immune and non-immune cells. [13] TLR5 recognizes bacterial flagellin, a principal component of bacterial flagella and a virulence factor. The activation of this receptor mobilizes the nuclear factor NF-κB and stimulates tumor necrosis factor-alpha production. [14]

TLR5 recognizes flagellin, [15] which is the protein monomer that makes up the filament of bacterial flagella, found on nearly all motile bacteria. There are highly conserved regions in the flagellin protein among all bacteria, facilitating the recognition of flagellin by a germ-line encoded receptor such as TLR5. [16] However, some Proteobacteria flagella have acquired mutations preventing their recognition by TLR5. [17]

Signaling pathway and regulation

The TLR5 signaling cascade is commonly triggered by the binding of bacterial flagellum to TLR5 on the cell surface. Binding of flagellum induces the dimerization of TLR5, which in turn recruits MyD88 and Mal/TIRAP. [18] [19] [20] The recruitment of MyD88 leads to subsequent activation of IRAK4, IRAK1, TRAF6, and eventually IκB kinases. [21] [22] Activation of IκB kinases contributes to the nuclear localization of NF-κB (a proinflammatory cytokine). NF-κB induces many downstream gene expressions, which initiates the canonical proinflammatory pathway. This TLR5/flagellum interaction results in different responses in difference cell types. In epithelial cells, binding of flagellum to TLR5 induces IL8 production. In human monocytes and dendritic cells, this interaction results in the secretion of proinflammatory cytokines such as TNF. [6]

Recent study has identified Caveolin-1 as a potential regulator of TLR5 expression. [23] In contrast to the decreased TLR4 level in senescent cells, TLR5 expression maintains relatively stable during the aging process, which is correlated with the high level of Caveolin-1 in aging cells. Data from Caveolin-1 knockout mice demonstrated that TLR5 expression significantly decreases in the absence of Caveolin-1 expression in aging cells. [23] It is hypothesized that the Caveolin-1 directly interacts with TLR5 to stabilize it and hence increases the level of TLR5.

Clinical significance

Inflammatory bowel disease

TLR5 may play a role in inflammatory bowel disease (IBD). TLR5-deficient mice develop spontaneous colitis [24] and metabolic syndrome which are associated with altered gut microbiota. [25] Statistically significant lower levels of TLR5 expression have been found in patients exhibiting moderate to severe ulcerative colitis (UC). In these patients, lower TLR5 mRNA levels were found along with decreased immunoreactivity of TLR5 in the inflamed mucosa of UC patients. [7]

Osteoclastogenesis and bone loss

Bone loss and osteoclastogenesis are induced by inflammation in infectious and autoimmune diseases. [10] A recent study has identified TLR5 as a novel mediator in the process of inflammation-induced bone loss and osteoclastogenesis. Flagellin, which is a TLR5-activating ligand, is present in synovial fluid from patients with rheumatoid arthritis. Activation of TLR5 in these patients leads to subsequent activation of receptor activator of NF-κB ligand (RANKL). Activation of RANKL leads to increased expression of osteoclastic genes. Activation of these genes results in robust osteoclast formation and bone loss. [10] This process is absent in TLR5 knockout mice model. [10]

Cancer

Gastric

Chronic inflammation in GI tract has been known to increase the risk of gastric cancer, with H. pylori being one of the most common resources of infection. [11] TLR5 is an essential factor in inducing inflammatory response to H. pylori infection. During infection, expression and ligation of TLR5 and TLR2 are required for the activation of proinflammatory cytokines such as NF-κB. [26] However, TLR5 interaction with H. pylori only induces weak TLR5 activation. The inflammatory response induced by TLR5 during H. pylori is also considered to be possibly flagellin independent. This suggests that an unknown H. pylori factor is responsible for this response [11] In addition to inflammation induction, TLR5 is also shown to enhance gastric cancer cell proliferation through an ERK-dependent pathway. [27] This is supported by the increased level of TLR5 expression from normal gastric mucosa to gastric cancer cells. [28]

Cervical

TLR5 is suggested to be possibly involved in HPV induced inflammation and subsequent cervical neoplasia formation. [12] TLR5 is generally absent in normal cervical squamous epithelium. However, a gradually increased level of TLR5 expression has been detected in low-grade cervical intraepithelial neoplasia (CIN), high grade CIN, and invasive cervical cancer. [29] However, the exact mechanism of interaction between TLR5 and HPV is not known.

Ovarian

It has been reported that TLR5 expression is detected in both ovarian epithelium and ovarian cancer cell lines but not in ovarian stroma, suggesting a possible role of TLR5 in inflammation induced ovarian cancer onset. [30]

Related Research Articles

Flagellins are a family of proteins present in flagellated bacteria which arrange themselves in a hollow cylinder to form the filament in a bacterial flagellum. Flagellin has a mass on average of about 40,000 daltons. Flagellins are the principal component of bacterial flagella that have a crucial role in bacterial motility.

<span class="mw-page-title-main">Toll-like receptor</span> Class of immune system proteins

Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system. They are single-spanning receptors usually expressed on sentinel cells such as macrophages and dendritic cells, that recognize structurally conserved molecules derived from microbes. Once these microbes have reached physical barriers such as the skin or intestinal tract mucosa, they are recognized by TLRs, which activate immune cell responses. The TLRs include TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TLR10, TLR11, TLR12, and TLR13. Humans lack genes for TLR11, TLR12 and TLR13 and mice lack a functional gene for TLR10. The receptors TLR1, TLR2, TLR4, TLR5, TLR6, and TLR10 are located on the cell membrane, whereas TLR3, TLR7, TLR8, and TLR9 are located in intracellular vesicles.

Pattern recognition receptors (PRRs) play a crucial role in the proper function of the innate immune system. PRRs are germline-encoded host sensors, which detect molecules typical for the pathogens. They are proteins expressed mainly by cells of the innate immune system, such as dendritic cells, macrophages, monocytes, neutrophils, as well as by epithelial cells, to identify two classes of molecules: pathogen-associated molecular patterns (PAMPs), which are associated with microbial pathogens, and damage-associated molecular patterns (DAMPs), which are associated with components of host's cells that are released during cell damage or death. They are also called primitive pattern recognition receptors because they evolved before other parts of the immune system, particularly before adaptive immunity. PRRs also mediate the initiation of antigen-specific adaptive immune response and release of inflammatory cytokines.

<span class="mw-page-title-main">IRAK4</span> Protein-coding gene in humans

IRAK-4, in the IRAK family, is a protein kinase involved in signaling innate immune responses from Toll-like receptors. It also supports signaling from T-cell receptors. IRAK4 contains domain structures which are similar to those of IRAK1, IRAK2, IRAKM and Pelle. IRAK4 is unique compared to IRAK1, IRAK2 and IRAKM in that it functions upstream of the other IRAKs, but is more similar to Pelle in this trait. IRAK4 has important clinical applications.

<span class="mw-page-title-main">MYD88</span> Protein found in humans

Myeloid differentiation primary response 88 (MYD88) is a protein that, in humans, is encoded by the MYD88 gene. originally discovered in the laboratory of Dan A. Liebermann as a Myeloid differentiation primary response gene.

<span class="mw-page-title-main">Alveolar macrophage</span>

An alveolar macrophage, pulmonary macrophage, is a type of macrophage, a professional phagocyte, found in the airways and at the level of the alveoli in the lungs, but separated from their walls.

<span class="mw-page-title-main">Toll-like receptor 2</span> Cell surface receptor found in humans

Toll-like receptor 2 also known as TLR2 is a protein that in humans is encoded by the TLR2 gene. TLR2 has also been designated as CD282. TLR2 is one of the toll-like receptors and plays a role in the immune system. TLR2 is a membrane protein, a receptor, which is expressed on the surface of certain cells and recognizes foreign substances and passes on appropriate signals to the cells of the immune system.

Pyroptosis is a highly inflammatory form of lytic programmed cell death that occurs most frequently upon infection with intracellular pathogens and is likely to form part of the antimicrobial response. This process promotes the rapid clearance of various bacterial, viral, fungal and protozoan infections by removing intracellular replication niches and enhancing the host's defensive responses. Pyroptosis can take place in immune cells and is also reported to occur in keratinocytes and some epithelial cells.

<span class="mw-page-title-main">TICAM1</span> Protein found in humans

TIR domain containing adaptor molecule 1 is an adapter in responding to activation of toll-like receptors (TLRs). It mediates the rather delayed cascade of two TLR-associated signaling cascades, where the other one is dependent upon a MyD88 adapter.

<span class="mw-page-title-main">Toll-like receptor 7</span> Protein found in humans

Toll-like receptor 7, also known as TLR7, is a protein that in humans is encoded by the TLR7 gene. Orthologs are found in mammals and birds. It is a member of the toll-like receptor (TLR) family and detects single stranded RNA.

<span class="mw-page-title-main">Toll-like receptor 4</span> Cell surface receptor found in humans

Toll-like receptor 4 (TLR4), also designated as CD284, is a key activator of the innate immune response and plays a central role in the fight against bacterial infections. TLR4 is a transmembrane protein of approximately 95 kDa that is encoded by the TLR4 gene.

<span class="mw-page-title-main">Toll-like receptor 6</span> Protein found in humans

Toll-like receptor 6 is a protein that in humans is encoded by the TLR6 gene. TLR6 is a transmembrane protein, member of toll-like receptor family, which belongs to the pattern recognition receptor (PRR) family. TLR6 acts in a heterodimer form with toll-like receptor 2 (TLR2). Its ligands include multiple diacyl lipopeptides derived from gram-positive bacteria and mycoplasma and several fungal cell wall saccharides. After dimerizing with TLR2, the NF-κB intracellular signalling pathway is activated, leading to a pro-inflammatory cytokine production and activation of innate immune response. TLR6 has also been designated as CD286.

<span class="mw-page-title-main">Toll-like receptor 8</span> Protein found in humans

Toll-like receptor 8 is a protein that in humans is encoded by the TLR8 gene. TLR8 has also been designated as CD288. It is a member of the toll-like receptor (TLR) family.

<span class="mw-page-title-main">Toll-like receptor 9</span> Protein found in humans

Toll-like receptor 9 is a protein that in humans is encoded by the TLR9 gene. TLR9 has also been designated as CD289. It is a member of the toll-like receptor (TLR) family. TLR9 is an important receptor expressed in immune system cells including dendritic cells, macrophages, natural killer cells, and other antigen presenting cells. TLR9 is expressed on endosomes internalized from the plasma membrane, binds DNA, and triggers signaling cascades that lead to a pro-inflammatory cytokine response. Cancer, infection, and tissue damage can all modulate TLR9 expression and activation. TLR9 is also an important factor in autoimmune diseases, and there is active research into synthetic TLR9 agonists and antagonists that help regulate autoimmune inflammation.

<span class="mw-page-title-main">Toll-like receptor 10</span> Protein-coding gene in the species Homo sapiens

Toll-like receptor 10 is a protein that in humans is encoded by the TLR10 gene. TLR10 has also been designated as CD290 . TLR10 has not been extensively studied because it is a pseudogene in mice, though all other mammalian species contain an intact copy of the TLR10 gene. Unlike other TLRs, TLR10 does not activate the immune system and has instead been shown to suppress inflammatory signaling on primary human cells. This makes TLR10 unique among the TLR family. TLR10 was thought to be an "orphan" receptor, however, recent studies have identified ligands for TLR10 and these include HIV-gp41. Ligands for TLR2 are potential ligands for TLR10.

<span class="mw-page-title-main">NOD-like receptor</span> Class of proteins

The nucleotide-binding oligomerization domain-like receptors, or NOD-like receptors (NLRs), are intracellular sensors of pathogen-associated molecular patterns (PAMPs) that enter the cell via phagocytosis or pores, and damage-associated molecular patterns (DAMPs) that are associated with cell stress. They are types of pattern recognition receptors (PRRs), and play key roles in the regulation of innate immune response. NLRs can cooperate with toll-like receptors (TLRs) and regulate inflammatory and apoptotic response.

Entolimod (CBLB502) is being developed by Cleveland Biolabs, Inc. for dual indications under the U.S. Food & Drug Administration’s (FDA) animal efficacy rule as a pivotal-stage radiation countermeasure, and under the FDA’s traditional drug approval pathway as a cancer treatment.

The lung microbiota is the pulmonary microbial community consisting of a complex variety of microorganisms found in the lower respiratory tract particularly on the mucous layer and the epithelial surfaces. These microorganisms include bacteria, fungi, viruses and bacteriophages. The bacterial part of the microbiota has been more closely studied. It consists of a core of nine genera: Prevotella, Sphingomonas, Pseudomonas, Acinetobacter, Fusobacterium, Megasphaera, Veillonella, Staphylococcus, and Streptococcus. They are aerobes as well as anaerobes and aerotolerant bacteria. The microbial communities are highly variable in particular individuals and compose of about 140 distinct families. The bronchial tree for instance contains a mean of 2000 bacterial genomes per cm2 surface. The harmful or potentially harmful bacteria are also detected routinely in respiratory specimens. The most significant are Moraxella catarrhalis, Haemophilus influenzae, and Streptococcus pneumoniae. They are known to cause respiratory disorders under particular conditions namely if the human immune system is impaired. The mechanism by which they persist in the lower airways in healthy individuals is unknown.

The interleukin-1 receptor (IL-1R) associated kinase (IRAK) family plays a crucial role in the protective response to pathogens introduced into the human body by inducing acute inflammation followed by additional adaptive immune responses. IRAKs are essential components of the Interleukin-1 receptor signaling pathway and some Toll-like receptor signaling pathways. Toll-like receptors (TLRs) detect microorganisms by recognizing specific pathogen-associated molecular patterns (PAMPs) and IL-1R family members respond the interleukin-1 (IL-1) family cytokines. These receptors initiate an intracellular signaling cascade through adaptor proteins, primarily, MyD88. This is followed by the activation of IRAKs. TLRs and IL-1R members have a highly conserved amino acid sequence in their cytoplasmic domain called the Toll/Interleukin-1 (TIR) domain. The elicitation of different TLRs/IL-1Rs results in similar signaling cascades due to their homologous TIR motif leading to the activation of mitogen-activated protein kinases (MAPKs) and the IκB kinase (IKK) complex, which initiates a nuclear factor-κB (NF-κB) and AP-1-dependent transcriptional response of pro-inflammatory genes. Understanding the key players and their roles in the TLR/IL-1R pathway is important because the presence of mutations causing the abnormal regulation of Toll/IL-1R signaling leading to a variety of acute inflammatory and autoimmune diseases.

<span class="mw-page-title-main">Bacterial therapy</span>

Bacterial therapy is the therapeutic use of bacteria to treat diseases. Bacterial therapeutics are living medicines, and may be wild type bacteria or bacteria that have been genetically engineered to possess therapeutic properties that is injected into a patient. Other examples of living medicines include cellular therapeutics, activators of anti-tumor immunity, or synergizing with existing tools and approaches. and phage therapeutics, or as delivery vehicles for treatment, diagnosis, or imaging, complementing or synergizing with existing tools and approaches.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000187554 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000079164 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Rock FL, Hardiman G, Timans JC, Kastelein RA, Bazan JF (January 1998). "A family of human receptors structurally related to Drosophila Toll". Proceedings of the National Academy of Sciences of the United States of America. 95 (2): 588–93. Bibcode:1998PNAS...95..588R. doi: 10.1073/pnas.95.2.588 . PMC   18464 . PMID   9435236.
  6. 1 2 Miao EA, Andersen-Nissen E, Warren SE, Aderem A (September 2007). "TLR5 and Ipaf: dual sensors of bacterial flagellin in the innate immune system". Seminars in Immunopathology. 29 (3): 275–88. doi:10.1007/s00281-007-0078-z. PMID   17690885. S2CID   21209470.
  7. 1 2 Stanislawowski M, Wierzbicki PM, Golab A, Adrych K, Kartanowicz D, Wypych J, et al. (October 2009). "Decreased Toll-like receptor-5 (TLR-5) expression in the mucosa of ulcerative colitis patients". Journal of Physiology and Pharmacology. 60 (Suppl 4): 71–5. PMID   20083854.
  8. ↑ Kim SJ, Chen Z, Chamberlain ND, Essani AB, Volin MV, Amin MA, Volkov S, Gravallese EM, Arami S, Swedler W, Lane NE, Mehta A, Sweiss N, Shahrara S (October 2014). "Ligation of TLR5 promotes myeloid cell infiltration and differentiation into mature osteoclasts in rheumatoid arthritis and experimental arthritis". Journal of Immunology. 193 (8). Baltimore, Md.: 3902–13. doi:10.4049/jimmunol.1302998. PMC   4185216 . PMID   25200955.
  9. ↑ Badr MT, Häcker G (2019). "Gene expression profiling meta-analysis reveals novel gene signatures and pathways shared between tuberculosis and rheumatoid arthritis". PLOS ONE. 14 (3): e0213470. Bibcode:2019PLoSO..1413470B. doi: 10.1371/journal.pone.0213470 . PMC   6405138 . PMID   30845171.
  10. 1 2 3 4 Kassem A, Henning P, Kindlund B, Lindholm C, Lerner UH (November 2015). "TLR5, a novel mediator of innate immunity-induced osteoclastogenesis and bone loss". FASEB Journal. 29 (11): 4449–60. doi: 10.1096/fj.15-272559 . PMID   26207027.
  11. 1 2 3 Castaño-Rodríguez N, Kaakoush NO, Mitchell HM (2014-01-01). "Pattern-recognition receptors and gastric cancer". Frontiers in Immunology. 5: 336. doi: 10.3389/fimmu.2014.00336 . PMC   4105827 . PMID   25101079.
  12. 1 2 Husseinzadeh N, Davenport SM (November 2014). "Role of toll-like receptors in cervical, endometrial and ovarian cancers: a review". Gynecologic Oncology. 135 (2): 359–63. doi:10.1016/j.ygyno.2014.08.013. PMID   25135000.
  13. ↑ Sharma N, Akhade AS, Qadri A (April 2013). "Sphingosine-1-phosphate suppresses TLR-induced CXCL8 secretion from human T cells". Journal of Leukocyte Biology. 93 (4): 521–8. doi: 10.1189/jlb.0712328 . PMID   23345392.
  14. ↑ "Entrez Gene: TLR5 toll-like receptor 5".
  15. ↑ Hayashi F, Smith KD, Ozinsky A, Hawn TR, Yi EC, Goodlett DR, et al. (April 2001). "The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5". Nature. 410 (6832): 1099–103. Bibcode:2001Natur.410.1099H. doi:10.1038/35074106. PMID   11323673. S2CID   4422702.
  16. ↑ Smith KD, Andersen-Nissen E, Hayashi F, Strobe K, Bergman MA, Barrett SL, et al. (December 2003). "Toll-like receptor 5 recognizes a conserved site on flagellin required for protofilament formation and bacterial motility". Nature Immunology. 4 (12): 1247–53. doi:10.1038/ni1011. PMID   14625549. S2CID   6157006.
  17. ↑ Andersen-Nissen E, Smith KD, Strobe KL, Barrett SL, Cookson BT, Logan SM, Aderem A (June 2005). "Evasion of Toll-like receptor 5 by flagellated bacteria". Proceedings of the National Academy of Sciences of the United States of America. 102 (26): 9247–52. Bibcode:2005PNAS..102.9247A. doi: 10.1073/pnas.0502040102 . PMC   1166605 . PMID   15956202.
  18. ↑ Gewirtz AT, Navas TA, Lyons S, Godowski PJ, Madara JL (August 2001). "Cutting edge: bacterial flagellin activates basolaterally expressed TLR5 to induce epithelial proinflammatory gene expression". Journal of Immunology. 167 (4): 1882–5. doi: 10.4049/jimmunol.167.4.1882 . PMID   11489966. S2CID   23844864.
  19. ↑ Choi YJ, Jung J, Chung HK, Im E, Rhee SH (January 2013). "PTEN regulates TLR5-induced intestinal inflammation by controlling Mal/TIRAP recruitment". FASEB Journal. 27 (1): 243–54. doi: 10.1096/fj.12-217596 . PMC   3528317 . PMID   23038756.
  20. ↑ Rhee SH, Kim H, Moyer MP, Pothoulakis C (July 2006). "Role of MyD88 in phosphatidylinositol 3-kinase activation by flagellin/toll-like receptor 5 engagement in colonic epithelial cells". The Journal of Biological Chemistry. 281 (27): 18560–8. doi: 10.1074/jbc.M513861200 . PMID   16644730.
  21. ↑ Gohda J, Matsumura T, Inoue J (September 2004). "Cutting edge: TNFR-associated factor (TRAF) 6 is essential for MyD88-dependent pathway but not toll/IL-1 receptor domain-containing adaptor-inducing IFN-beta (TRIF)-dependent pathway in TLR signaling". Journal of Immunology. 173 (5): 2913–7. doi: 10.4049/jimmunol.173.5.2913 . PMID   15322147.
  22. ↑ Moors MA, Li L, Mizel SB (July 2001). "Activation of interleukin-1 receptor-associated kinase by gram-negative flagellin". Infection and Immunity. 69 (7): 4424–9. doi:10.1128/IAI.69.7.4424-4429.2001. PMC   98515 . PMID   11401982.
  23. 1 2 Lim JS, Nguyen KC, Han JM, Jang IS, Fabian C, Cho KA (December 2015). "Direct Regulation of TLR5 Expression by Caveolin-1". Molecules and Cells. 38 (12): 1111–7. doi:10.14348/molcells.2015.0213. PMC   4697003 . PMID   26615831.
  24. ↑ Singh V, Yeoh BS, Carvalho F, Gewirtz AT, Vijay-Kumar M (July 2015). "Proneness of TLR5 deficient mice to develop colitis is microbiota dependent". Gut Microbes. 6 (4): 279–83. doi:10.1080/19490976.2015.1060390. PMC   4615783 . PMID   26067589.
  25. ↑ Vijay-Kumar M, Aitken JD, Carvalho FA, Cullender TC, Mwangi S, Srinivasan S, et al. (April 2010). "Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5". Science. 328 (5975): 228–31. Bibcode:2010Sci...328..228V. doi:10.1126/science.1179721. PMC   4714868 . PMID   20203013.
  26. ↑ Smith MF, Mitchell A, Li G, Ding S, Fitzmaurice AM, Ryan K, et al. (August 2003). "Toll-like receptor (TLR) 2 and TLR5, but not TLR4, are required for Helicobacter pylori-induced NF-kappa B activation and chemokine expression by epithelial cells". The Journal of Biological Chemistry. 278 (35): 32552–60. doi: 10.1074/jbc.M305536200 . PMID   12807870.
  27. ↑ Song EJ, Kang MJ, Kim YS, Kim SM, Lee SE, Kim CH, et al. (July 2011). "Flagellin promotes the proliferation of gastric cancer cells via the Toll-like receptor 5". International Journal of Molecular Medicine. 28 (1): 115–9. doi: 10.3892/ijmm.2011.656 . PMID   21455558.
  28. ↑ Pimentel-Nunes P, Afonso L, Lopes P, Roncon-Albuquerque R, Gonçalves N, Henrique R, et al. (September 2011). "Increased expression of toll-like receptors (TLR) 2, 4 and 5 in gastric dysplasia". Pathology & Oncology Research. 17 (3): 677–83. doi:10.1007/s12253-011-9368-9. PMID   21455638. S2CID   762206.
  29. ↑ Lee JW, Choi JJ, Seo ES, Kim MJ, Kim WY, Choi CH, et al. (November 2007). "Increased toll-like receptor 9 expression in cervical neoplasia". Molecular Carcinogenesis. 46 (11): 941–7. doi:10.1002/mc.20325. PMID   17440926. S2CID   29324508.
  30. ↑ Zhou M, McFarland-Mancini MM, Funk HM, Husseinzadeh N, Mounajjed T, Drew AF (September 2009). "Toll-like receptor expression in normal ovary and ovarian tumors". Cancer Immunology, Immunotherapy. 58 (9): 1375–85. doi:10.1007/s00262-008-0650-y. PMID   19184006. S2CID   23677988.

Further reading

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.