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- BLP, bacterial lipoprotein
- IFN, interferon
- IL, interleukin
- OVA, ovalbumin
- TLR, toll-like receptor
- Th, T helper
- TGF, transforming growth factor
Toll-like receptors (TLRs) are a family of proteins that are involved in the initial phase of host defence against invading pathogens. TLRs act as primary sensors of microbial products and activate signalling pathways that lead to the induction of immune and inflammatory genes.1 TLRs belong to a broader family of proteins, which include receptors for the proinflammatory cytokines interleukin (IL)-1 and IL-18. All members of this superfamily signal inflammation in a similar manner. This is due to the presence of a conserved protein sequence in the cytosolic domain called the Toll–IL-1 receptor (TIR) domain, which activates common signalling pathways, most notably those leading to the activation of the transcription factor NF-κB (nuclear factor κB) and stress-activated protein kinases.2 Most investigations on TLRs have focused on cells of the innate system. Furthermore, most research on the biological implications of TLRs has centred on infections. This is because the patterns recognised by TLRs are principally from pathogens. We have investigated the potential role of TLRs in an inflammatory disease, asthma.
Asthma is a chronic inflammatory condition of the airways characterised by airway hyperresponsiveness, inflammatory infiltrates in the bronchial wall containing eosinophils, and elevated serum IgE levels. T helper (Th) 2 lymphocytes are thought to play a key role in the initiation and perpetuation of this airway inflammation.3–5 The prevalence of asthma and allergies has increased dramatically over the past 20 years in developed countries, which cannot be explained by changes in genetic predisposition. Environmental factors, especially in industrialised countries, are now thought to be responsible for this rapid increase in asthma.6,7
We summarise here our recent data showing that a TLR2 agonist, BLP (bacterial lipoprotein, Pam3CSK4) is highly effective in treating an established murine model of OVA specific asthma.
BLP REVERSES ESTABLISHED OVA INDUCED AIRWAYS INFLAMMATION
To investigate the therapeutic potential of BLP in …
Footnotes
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This study received financial support from the Medical Research Council, the Wellcome Trust, The Chief Scientist Office of Scotland and the European Commission.
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Competing interests: none declared