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Publication : Potential down-regulation of salivary gland AQP5 by LPS via cross-coupling of NF-kappaB and p-c-Jun/c-Fos.

First Author  Yao C Year  2010
Journal  Am J Pathol Volume  177
Issue  2 Pages  724-34
PubMed ID  20522648 Mgi Jnum  J:163414
Mgi Id  MGI:4821910 Doi  10.2353/ajpath.2010.090282
Citation  Yao C, et al. (2010) Potential down-regulation of salivary gland AQP5 by LPS via cross-coupling of NF-kappaB and p-c-Jun/c-Fos. Am J Pathol 177(2):724-34
abstractText  The mRNA and protein levels of aquaporin (AQP)5 in the parotid gland were found to be potentially decreased by lipopolysaccharide (LPS) in vivo in C3H/HeN mice, but only weakly in C3H/HeJ, a TLR4 mutant mouse strain. In the LPS-injected mice, pilocarpine-stimulated saliva production was reduced by more than 50%. In a tissue culture system, the LPS-induced decrease in the AQP5 mRNA level was blocked completely by pyrrolidine dithiocarbamate, MG132, tyrphostin AG126, SP600125, and partially by SB203580, which are inhibitors for IkappaB kinase, 26S proteasome, ERK1/2, JNK, and p38 MAPK, respectively. In contrast, the expression of AQP1 mRNA was down-regulated by LPS and such down-regulation was blocked only by SP600125. The transcription factors NF-kappaB (p65 subunit), p-c-Jun, and c-Fos were increased by LPS given in vivo, whereas the protein-binding activities of the parotid gland extract toward the sequences for NF-kappaB but not AP-1-responsive elements present at the promoter region of the AQP5 gene were increased by LPS injection. Co-immunoprecipitation by using antibody columns suggested the physical association of the three transcription factors. These results suggest that LPS-induced potential down-regulation of expression of AQP5 mRNA in the parotid gland is mediated via a complex(es) of these two classes of transcription factors, NF-kappaB and p-c-Jun/c-Fos.
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