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char = .;code = 46
result sql = Src kinase participates in LPS-induced activation of NADPH oxidase.
Src kinase participates in LPS-induced activation of NADPH oxidase.
char = T;code = 84
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char = ;code = 32
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char = o;code = 111
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char = P;code = 80
char = H;code = 72
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char = T;code = 84
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char = e;code = 101
char = ;code = 32
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char = a;code = 97
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char = i;code = 105
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
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char = A;code = 65
char = D;code = 68
char = P;code = 80
char = H;code = 72
char = ;code = 32
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char = R;code = 82
char = A;code = 65
char = W;code = 87
char = 2;code = 50
char = 6;code = 54
char = 4;code = 52
char = .;code = 46
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char = c;code = 99
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char = r;code = 114
char = o;code = 111
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char = n;code = 110
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char = f;code = 102
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char = i;code = 105
char = l;code = 108
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char = o;code = 111
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char = P;code = 80
char = H;code = 72
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char = o;code = 111
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char = L;code = 76
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char = a;code = 97
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char = P;code = 80
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result sql = The production of superoxide from NADPH oxidase by macrophages in response to endotoxin (LPS) is an important innate immune response, yet it is not clear how LPS signals the activation of NADPH oxidase. The hypothesis is that LPS-induced src kinase and PI3 kinase (PI3K) facilitates the activation of p47(phox), the regulatory subunit of NADPH oxidase. In mouse macrophage RAW264.7 cells, inhibition of src tyrosine family kinases inhibited LPS-induced activation of NADPH oxidase, phosphorylation of p47(phox), activation of PI3K and phosphorylation of the TLR4. Moreover, inhibition of LPS-induced increases in intracellular calcium blunted src kinase activation, PI3K association with TLR4, as well as PI3 kinase activation. These data suggest that both src kinase and PI3 kinase are involved in LPS-induced NADPH oxidase activation. Importantly, these data suggest that LPS-induced src kinase activation is critical for PI3 kinase activation as well as TLR4 phosphorylation and is dependent upon LPS-induced increase in intracellular calcium. These signaling events fill critical gaps in our understanding of LPS-induced free radical production as well as may potentially responsible for the mechanism of innate immune tolerance or desensitization caused by steroids or ethanol.

Publication: Mol. Immunol. 2010 Jan ;47(4)::756-62. :doi: 10.1016/j.molimm.2009.10.012.
Publication Date: 2010 Jan
Study Author(s): Check, Jennifer;Byrd, Christy L;Menio, Jade;Rippe, Richard A;Hines, Ian N;Wheeler, Michael D;
Institution: Department of Medicine, University of North Carolina, Chapel Hill, NC 27599, United States.
Shortcut link to this study:
The production of superoxide from NADPH oxidase by macrophages in response to endotoxin (LPS) is an important innate immune response, yet it is not clear how LPS signals the activation of NADPH oxidase. The hypothesis is that LPS-induced src kinase and PI3 kinase (PI3K) facilitates the activation of p47(phox), the regulatory subunit of NADPH oxidase. In mouse macrophage RAW264.7 cells, inhibition of src tyrosine family kinases inhibited LPS-induced activation of NADPH oxidase, phosphorylation of p47(phox), activation of PI3K and phosphorylation of the TLR4. Moreover, inhibition of LPS-induced increases in intracellular calcium blunted src kinase activation, PI3K association with TLR4, as well as PI3 kinase activation. These data suggest that both src kinase and PI3 kinase are involved in LPS-induced NADPH oxidase activation. Importantly, these data suggest that LPS-induced src kinase activation is critical for PI3 kinase activation as well as TLR4 phosphorylation and is dependent upon LPS-induced increase in intracellular calcium. These signaling events fill critical gaps in our understanding of LPS-induced free radical production as well as may potentially responsible for the mechanism of innate immune tolerance or desensitization caused by steroids or ethanol.
PMID: 19942291

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