Potential down-regulation of salivary gland AQP5 by LPS via cross-coupling of NF-kappaB and p-c-Jun/c-Fos.
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.
Department of Molecular Oral Physiology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima-shi, Tokushima, Japan.
Chenjuan
C
Yao
Nunuk
N
Purwanti
Mileva Ratko
MR
Karabasil
Ahmad
A
Azlina
Purevjav
P
Javkhlan
Takahiro
T
Hasegawa
Tetsuya
T
Akamatsu
Toru
T
Hosoi
Koichiro
K
Ozawa
Kazuo
K
Hosoi
D000818:Animals; D051398:Aquaporin 1 / Q000235:genetics / Q000378:metabolism; D051402:Aquaporin 5 / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D012469:Salivary Glands / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*
D051402:Aquaporin 5; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009566:Nitrates; D009573:Nitrites; D016760:Proto-Oncogene Proteins c-fos; D051398:Aquaporin 1; D048031:JNK Mitogen-Activated Protein Kinases