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• W2154271415 endingPage "6658" @default.
• W2154271415 startingPage "6650" @default.
• W2154271415 abstract "ABSTRACT Toll-like receptor 4 (TLR4) mediates the response to lipopolysaccharide, and its activation induces the expression of a large number of inflammatory genes, many of which are also induced by other pathogen-associated molecular patterns. Interestingly, the subset of genes that are dependent on TLR4 for optimal expression during gram-negative bacterial infection has not been determined. We have previously shown that TLR4-deficient mice rapidly develop acute pneumonia after inoculation with Bordetella bronchiseptica , suggesting that TLR4 is required for expression of early elicited gene products in this model. Microarray analysis with macrophages derived from wild-type and TLR4-deficient mice was used to identify genes whose expression, within 1 h of bacterial exposure, is dependent on TLR4. The results of this investigation suggest that TLR4 is not required for the majority of the transcriptional response to B. bronchiseptica . However, early tumor necrosis factor alpha (TNF-α) mRNA expression is primarily dependent on TLR4 and in vitro and in vivo protein levels substantiate this finding. TLR4-deficient mice and TNF-α −/− mice are similarly susceptible to infection with relatively low doses of B. bronchiseptica and in vivo neutralization studies indicate that it is the TLR4-dependent early elicited TNF-α response that is critical for preventing severe pneumonia and limiting bacterial growth. These results suggest that one critical role for TLR4 is the generation of a robust but transient TNF-α response that is critical to innate host defense during acute gram-negative respiratory infection." @default.
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• W2154271415 date "2004-11-01" @default.
• W2154271415 modified "2023-10-11" @default.
• W2154271415 title "Toll-Like Receptor 4-Dependent Early Elicited Tumor Necrosis Factor Alpha Expression Is Critical for Innate Host Defense against<i>Bordetella bronchiseptica</i>" @default.
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• W2154271415 doi "https://doi.org/10.1128/iai.72.11.6650-6658.2004" @default.
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