EurekaMag
+ Translate
+ Most Popular
Gaucher's disease;thirty-two years experience at Siriraj Hospital
A study of Macrobathra Meyrick from China (Lepidoptera, Cosmopterigidae)
First occurrence in ores of tetragonal chalcocite
Effects of trace element nutrition on sleep patterns in adult women
N.Z. range management guidelines. 2. Design of grazing management systems for tussock country
A case of lipoma of the esophagus
A revision of world Acanthosomatidae (Heteroptera: Pentatomidae): keys to and descriptions of subfamilies, tribes and genera, with designation of types
Life history of the coronate scyphozoan Linuche unguiculata (Swartz, 1788)
Perceptual restoration of obliterated sounds
Mutagenicity studies on two chromium(III) coordination compounds
The formation of the skeleton. I. Growth of a long bone. 1st appearance of a center of calcification
Leucopenia and abnormal liver function in travellers on malaria chemoprophylaxis
The joint commission: four key root causes loom large in sentinel event data
Treatment of vitiligo with topical 15% lactic acid solution in combination with ultra violet-A
Behaviour of dairy cows within three hours after feed supply: I. Influence of housing type and time elapsing after feed supply
Observations of the propagation velocity and formation mechanism of burst fractures caused by gunshot
Management and control of patients with type 2 diabetes mellitus in Lebanon: results from the International Diabetes Management Practices Study (IDMPS)
The diet composition and nutritional knowledge of patients with anorexia nervosa
Physoporella croatica Herak, 1958 of the Slovak karst Anisian (Slovakia, the West Carpathians Mts.)
Bright lights, big noise. How effective are vehicle warning systems?
Ein Plesiosaurier-Rest mit Magensteinen aus mittlerem Lias von Quedlinburg
Incidence of Chlamydia trachomatis in patients with sterility
Monster soup: the microscope and Victorian fantasy
Preliminary tests with residual sprays against poultry lice
Duration of the life of plants in phylogeny

Cooperation of Toll-like receptor 2 and 6 for cellular activation by soluble tuberculosis factor and Borrelia burgdorferi outer surface protein A lipoprotein: role of Toll-interacting protein and IL-1 receptor signaling molecules in Toll-like receptor 2 signaling


Cooperation of Toll-like receptor 2 and 6 for cellular activation by soluble tuberculosis factor and Borrelia burgdorferi outer surface protein A lipoprotein: role of Toll-interacting protein and IL-1 receptor signaling molecules in Toll-like receptor 2 signaling



Journal of Immunology 167(2): 987-994



ISSN/ISBN: 0022-1767

PMID: 11441107

DOI: 10.4049/jimmunol.167.2.987

Toll-like receptor 2 (TLR2) and TLR4 play important roles in innate immune responses to various microbial agents. We have previously shown that human dermal endothelial cells (HMEC) express TLR4, but very little TLR2, and respond to LPS, but not to Mycobacterium tuberculosis 19-kDa lipoprotein, unless transfected with TLR2. Here we report that HMEC are unresponsive to several additional biologically relevant TLR2 ligands, including, phenol-soluble modulin (PSM), a complex of three small secreted polypeptides from the skin commensal Staphylococcus epidermidis, soluble tuberculosis factor (STF), and Borrelia burgdorferi outer surface protein A lipoprotein (OspA-L). Expression of TLR2 renders HMEC responsive to all these ligands. We further characterized the signaling pathway in response to STF, OspA-L, and PSM in TLR2-transfected HMEC. The TLR2 signaling pathway for NF-kappaB trans-activation shares the IL-1R signaling molecules. Dominant negative constructs of TLR2 or TLR6 inhibit the responses of STF and OspA-L as well as PSM in TLR2-transfected HMEC, supporting the concept of functional cooperation between TLR2 and TLR6 for all these TLR2 ligands. Moreover, we show that Toll-interacting protein (Tollip) coimmunoprecipitates with TLR2 and TLR4 using HEK 293 cells, and overexpression of Tollip inhibits NF-kappaB activation in response to TLR2 and TLR4 signaling. Collectively, these findings suggest that there is functional interaction between TLR2 and TLR6 in the cellular response to STF and OspA-L in addition to S. epidermidis (PSM) Ags, and that engagement of TLR2 triggers a signaling cascade, which shares the IL-1R signaling molecules, similar to the TLR4-LPS signaling cascade. Our data also suggest that Tollip may be an important constituent of both the TLR2 and TLR4 signaling pathways.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 017833101

Download citation: RISBibTeXText

Related references

Cooperation between toll-like receptor 2 and TLR6 in phenol soluble modulin -induced NF-kB activation in human dermal endothelial cell Role of toll-interacting protein Tollip in TLR2 and TLR4 signaling. Pediatric Research 49(4 Part 2): 246A, 2001

Phagocytosis plays a dual role in activating dendritic cells; digestive production of active Toll-like receptor ligands and cooperation with Toll-like receptor signaling. Drug Discoveries and Therapeutics 4(2): 135-143, 2010

Toll-like receptor expression in human keratinocytes: nuclear factor kappaB controlled gene activation by Staphylococcus aureus is toll-like receptor 2 but not toll-like receptor 4 or platelet activating factor receptor dependent. Journal of Investigative Dermatology 121(6): 1389-1396, 2003

Regulation of Hepatic Drug-Metabolizing Enzyme Genes by Toll-Like Receptor 4 Signaling Is Independent of Toll-lnterleukin 1 Receptor Domain-Containing Adaptor Protein. Drug Metabolism and Disposition 36(1): 95-101, 2008

Regulation of hepatic drug-metabolizing enzyme genes by Toll-like receptor 4 signaling is independent of Toll-interleukin 1 receptor domain-containing adaptor protein. Drug Metabolism and Disposition: the Biological Fate of Chemicals 36(1): 95-101, 2008

Levocetrizine has anti-inflammatory effects against Toll-like receptor (TLR)3 through the inhibition of Toll-IL-1 receptor (TIR)-domain-containing adapter inducing IFN-beta (TRIF) and receptor-interacting protein (RIP). Auris Nasus Larynx 38(4): 474-479, 2011

Chondrocyte innate immune myeloid differentiation factor 88-dependent signaling drives procatabolic effects of the endogenous Toll-like receptor 2/Toll-like receptor 4 ligands low molecular weight hyaluronan and high mobility group box chromosomal protein 1 in mice. Arthritis and Rheumatism 62(7): 2004-2012, 2010

Poxviral protein A46 antagonizes Toll-like receptor 4 signaling by targeting BB loop motifs in Toll-IL-1 receptor adaptor proteins to disrupt receptor:adaptor interactions. Journal of Biological Chemistry 287(27): 22672-22682, 2012

Toll/Il-1 Receptor Domain-Containing Adaptor Inducing Ifn- (Trif) Associates with Tnf Receptor-Associated Factor 6 and Tank-Binding Kinase 1, and Activates Two Distinct Transcription Factors, Nf-B and Ifn-Regulatory Factor-3, in the Toll-Like Receptor Signaling. The Journal of Immunology 171(8): 4304-4310, 2003

Toll/IL-1 Receptor Domain-Containing Adaptor Inducing IFN-b (TRIF) Associates with TNF Receptor-Associated Factor 6 and TANK-Binding Kinase 1, and Activates Two Distinct Transcription Factors, NF-kB and IFN-Regulatory Factor-3, in the Toll-Like Receptor Signaling. Journal of Immunology 171(8): 04-10, 2003

Lipopolysaccharide increases Toll-like receptor 4 and downstream Toll-like receptor signaling molecules expression in bovine endometrial epithelial cells. Veterinary Immunology and Immunopathology 151(1-2): 20-27, 2013

Toll/IL-1 receptor domain-containing adaptor inducing IFN-beta (TRIF) associates with TNF receptor-associated factor 6 and TANK-binding kinase 1, and activates two distinct transcription factors, NF-kappa B and IFN-regulatory factor-3, in the Toll-like receptor signaling. Journal of Immunology 171(8): 4304-4310, 2003

Bruton's Tyrosine Kinase Is a Toll/Interleukin-1 Receptor Domain-binding Protein That Participates in Nuclear Factor kB Activation by Toll-like Receptor 4. The Journal of Biological Chemistry 278(28): 258-64, 2003

Bruton's tyrosine kinase is a Toll/interleukin-1 receptor domain-binding protein that participates in nuclear factor kappaB activation by Toll-like receptor 4. Journal of Biological Chemistry 278(28): 26258-26264, 2003

Toll/interleukin-1 receptor domain dimers as the platform for activation and enhanced inhibition of Toll-like receptor signaling. Journal of Biological Chemistry 287(37): 30993-31002, 2012