Naslov
The Importance of MD-2 in the Induction of TLR-4 Signaling and Release of Inflammatory Cytokines in Lungs

Autori
Hađina, Suzana , Weiss, Jerrold P., McCray, Paul B. Jr., Widstrom, Richard, Thorne, Peter S.

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
American Journal of Respiratory and Critical Care Medicine, Abstracts issue / - New York (NY) : American Thoracic Society (ATS), 2007

Skup
ATS 2007 International Conference

Mjesto i datum
San Francisco (CA), Sjedinjene Američke Države, 18.05.2007. - 23.05.2007

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
MD-2; TLR-4 signalling; lung inflammation

Sažetak
Rationale: Myeloid-secreted protein (MD-2) is required for Toll-like receptor (TLR) 4-dependent pro-inflammatory signaling by Gram-negative bacterial endotoxin. Our goal in this study was to determine whether MD-2 is necessary for endotoxin responses in lungs in vivo. For this purpose, we used MD-2 knockout and TLR-4 mutant mice. Methods: MD-2 null (C57/BL6 MD-2-/-), TLR-4 mutant (C3H/HeJ) and endotoxin-responsive (BALB/c) mice were exposed by nasal aspiration to purified aggregates of Neisseria meningitidis endotoxin (lipooligosaccharide ; LOSagg) or to a monomeric complex of LOS with MD-2 (LOS:MD-2), each at 300 EU/mouse. Four hours after the administration, total cell count, differentials and concentration of TNF-α and MIP-1α were evaluated in bronchoalveolar lavage. Results: The number of total cells and neutrophils was significantly higher in LOS treated BALB/c mice (1240x103 and 1144 x103) than in TLR-4 mutants (176x103 and 38.5x103) and MD-2 null mice (150x103 and 24.1x103). Moreover, the concentration of TNF-α and MIP-1α was markedly reduced in TLR-4 mutants and MD-2 null mice (115 pg/mL and 200 pg/mL vs. 85 pg/mL and 42 pg/mL) in comparison with BALB/c mice (6107 pg/mL and 5925 pg/mL). When treated with LOS:MD-2 complex MD-2 null mice showed stronger inflammatory responses than TLR-4 mutant in the number of neutrophils (495x103 vs. 75x103), concentration of TNF-α (1012 vs. 106 pg/mL) and MIP-1α (892 vs. 176 pg/mL). Conclusions: Mice with the TLR-4 mutation or without expression of MD-2 were hyporesponsive to nasally instilled endotoxin compared with wild type mice. The defect in endotoxin responsiveness of MD-2 null but not TLR4 mutant mice could be partially overcome by presentation of endotoxin as a preformed complex with MD-2. These data demonstrate that lung inflammatory responses depend on the presence of MD-2 as well as TLR4. Funded By: NIH P30 ES05605

Izvorni jezik
Engleski

Znanstvena područja
Javno zdravstvo i zdravstvena zaštita, Veterinarska medicina

Napomena
Rad je bio poster discussion sekcija

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