Human parotid saliva contains soluble toll-like receptor (TLR) 2 and modulates TLR2-mediated interleukin-8 production by monocytic cells

Kuroishi, Toshinobu; Tanaka, Yukinori; Sakai, Azusa; Sugawara, Yumiko; Komine, Ken Ichi; Sugawara, Shunji

doi:10.1016/j.molimm.2006.09.028

Cited by 47 publications

(58 citation statements)

References 32 publications

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“…Our results are slightly different from the previous reports, which communicate that the sTLR2 system is comprised of six polypeptides (83, 66, 50, 40, 38 and 25 kDa) in human breast milk and plasma (15), and three polypeptides (55,40, and 27 kDA) in the human parotid saliva (14). In our study we showed that the 98-kDa polypeptide corresponds to the full-length transmembrane TLR2 by using as control placental villous tissue, which lacks the two amniotic fluid isoforms attributable to sTLR2.…”

Section: Discussioncontrasting

confidence: 99%

“…A closer look at the data suggests that the 66-, 50-, 40-, and 25-kDa polypeptides continue to be detectable in human plasma even after preincubation of the anti-TLR2 polyclonal Ab with the blocking peptide (15). Similar findings are applicable to the 55-and 27-kDa polypeptides in human saliva (14). Second, cleavage and processing of the TLR2 full-length receptor may occur differently in amniotic fluid compared with human breast milk, plasma, or saliva.…”

Section: Discussionmentioning

confidence: 59%

“…Traditionally, activation of the inflammatory response occurs as a result of direct binding of cytokines and PAMPs to their specific membrane cytokine receptors or TLRs, respectively. However, recent experimental data suggest that many of the biological activities assigned to cytokines, PAMPs, and TLRs are mediated via naturally occurring soluble receptor factors for IL-6 (sIL-6R), TNF-␣ (sTNFR-1, sTNFR-2), CD14 (sCD14), LPS (LPS-binding protein), ubiquitin (amniotic fluid peptide-1), receptor for advanced glycation end-products (sRAGE), TLR4 (sTLR4), and TLR2 (sTLR2) (14,15,(45)(46)(47)(48).…”

Section: Discussionmentioning

confidence: 99%

“…Presence of TLR2 in the human placenta, deciduas, and amniochorion led us to question whether sTLR2 (14,15) is present in human amniotic fluid and modulates the level of TLR2 activation. Herein, we report for the first time that two sTLR2 polypeptides are detected in human amniotic fluid and placental villous explant supernatant.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, it has been suggested that the biological activity of the TLRs is not exclusively dependent on PAMPs, but is also regulated by co-receptor molecules (CD14), intracellular signaling adaptors (MyD88, Mal, TRIF, TRAM, and SARM), and soluble receptor antagonists (13). Specifically, it was shown that saliva, human plasma, and breast milk's TLR2-mediated innate immune activity can be altered through a natural soluble TLR2 (sTLR2) polypeptide (14,15). Although still unknown, it is thought that the sTLR2 peptide The costs of publication of this article were defrayed in part by the payment of page charges.…”

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confidence: 99%

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Soluble TLR2 Is Present in Human Amniotic Fluid and Modulates the Intraamniotic Inflammatory Response to Infection

Dulay

Buhimschi

Zhao

et al. 2009

The Journal of Immunology

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TLRs are pattern recognition transmembrane receptors that play key roles in innate immunity. A recently discovered soluble truncated form of TLR2 (sTLR2) acts as a decoy receptor, down-regulating the host inflammatory response to bacteria. To identify the presence and functional role of sTLR2 in modulating the intraamniotic inflammatory response to infection, we studied 109 amniotic fluid samples of women with normal pregnancy outcomes (n ‫؍‬ 28) and women with (n ‫؍‬ 39) and without (n ‫؍‬ 42) intraamniotic infection. We sought to demonstrate a functional role of the amniotic fluid sTLR2 in modulating the TLR2 inflammatory signaling in vitro by using a villous explant system. Two sTLR2 forms were identified, and specificity was confirmed with neutralizing peptides. We showed that sTLR2 is present constitutively in amniotic fluid, its levels are gestational age dependent, and we determined that the sTLR2 quantity and functional engagement modulates the intensity of the intraamniotic inflammation elicited by Gram-positive bacteria. In vitro, we demonstrated that challenging placental villous explants with a specific TLR2 agonist (Pam3Cys) induced a significant cytokine response. Notably, preincubation of the preterm, but not near-term, amniotic fluid with Pam3Cys significantly inhibited the ability of this TLR2 agonist to elicit a cytokine reaction. Moreover, depletion of sTLR2 from preterm amniotic fluid removed its neutralizing property. Monensin significantly diminished sTLR2 immunoreactivity, indicating that sTLR2 is the result of intracellular posttranslational processing of TLR2. We conclude that sTLR2 is part of the amniotic fluid innate immune system and participates in regulating the inflammatory response to microbial pathogens. The Journal of Immunology, 2009, 182: 7244 -7253.T he innate immune system is an archaic defense mechanism, phylogenetically preserved to be at the forefront of resistance to microbial infections (1). The human TLRs are essential for triggering an inflammatory innate immune response (2). To date, 13 mammalian TLRs have been identified and 10 of these are present in humans (3). At the maternal-fetal interface, TLRs are expressed not only in immune cells, but also in the trophoblast and decidual cells (4, 5). Moreover, their expression pattern varies according to the stage of pregnancy (5). Such findings provide evidence that during pregnancy, placental TLRs may play a key role in modulating the inflammatory response triggered by infection.TLRs are transmembrane receptors that mediate host defense through the engagement of pathogen-associated molecular patterns (PAMPs) 3 , which are ubiquitous constituents of the bacterial wall (6). TLR2 was the first of 10 human TLRs, proven to be precisely involved in recognition of PAMPs (lipoproteins, peptidoglycan, glycolipids, nucleic acids), representing broad groups of microbial species such as Gram-positive bacteria, Mycobacteria, spirochetes, and Mycoplasmataceae (7,8,9). Traditionally, it has been thought that the extracellular recepto...

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Soluble TLR2 Is Present in Human Amniotic Fluid and Modulates the Intraamniotic Inflammatory Response to Infection

Dulay

Buhimschi

Zhao

et al. 2009

The Journal of Immunology

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Odontoblasts in the dental pulp immune response

et al. 2008

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Recent studies have demonstrated that human dental pulp cells sense pathogens and elicit innate and/or adaptive immunity. Particular attention has been paid to odontoblasts that are situated at the pulp-dentin interface and constitute the first line of defense to cariogenic bacteria entering dentin after enamel disruption. In this review, recent in vitro and in vivo data suggesting that odontoblasts initiate immune/inflammatory events within the dental pulp in response to cariogenic bacteria are discussed. These data include sensing of pathogens by Toll-like receptors (TLRs), production of chemokines upon cell stimulation with microbial by-products and induction of dendritic cell migration. Additional results presented here reveal that all TLR genes are expressed in the healthy human dental pulp that is thus well equipped to combat pathogens entering the tissue. Seventeen chemokine genes including CXCL12, CCL2, CXCL9, CX3CL1, CCL8, CXCL10, CCL16, CCL5, CXCL2, CCL4, CXCL11 and CCL3, and 9 chemokine receptor genes including CXCR4, CCR1, CCR5, CX3CR1, CCR10 and CXCR3, are also expressed in pulp. TLR2, CCL2 and CXCL1 are upregulated in odontoblasts both under caries lesions and upon stimulation with pathogen by-products. These molecules thus appear as preferential targets for the design of therapeutic agents able to reduce the immune/inflammatory response to cariogenic bacteria and favor pulp healing.

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