JOURNAL ARTICLE

Role of NF-kappaB and p38 MAP kinase signaling pathways in the lipopolysaccharide-dependent activation of heme oxygenase-1 gene expression

Nastiti Wijayanti, Sebastian Huber, Anatoly Samoylenko, Thomas Kietzmann, Stephan Immenschuh
Antioxidants & Redox Signaling 2004, 6 (5): 802-10
15345139
Heme oxygenase (HO)-1 is the inducible isoform of the rate-limiting enzyme of heme degradation, which is up-regulated by a host of stress stimuli. The bacterial cell membrane component lipopolysaccharide (LPS) is a prototypical activator of monocytic cells. Here, it is shown that LPS induced the endogenous HO-1 gene expression in RAW264.7 monocytic cells. To investigate the molecular mechanisms of HO-1 gene induction by LPS, we performed transfection experiments with reporter gene constructs containing sequences of the proximal rat HO-1 gene promoter. Deletion and mutation analysis indicated that a cyclic AMP response element/activator protein-1 site (-664/-657), but not an E-box motif (-47/-42), played a major role for LPS-dependent HO-1 gene induction. Up-regulation of HO-1 promoter activity by LPS was decreased by pharmacological nuclear factor-kappaB (NF-kappaB) inhibitors and by cotransfected expression vectors with dominant negative isoforms of NF-kappaB-inducing kinase, inhibitor of NF-kappaB (IkappaB) kinase beta, and IkappaBalpha. Moreover, the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 and overexpressed dominant negative p38beta decreased, whereas dominant negative p38delta increased, LPS-dependent induction of HO-1 gene expression. The results suggest that the NF-kappaB and p38 MAPK signaling pathways mediate the LPS-dependent induction of HO-1 gene expression via DNA sequences of the proximal promoter region.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
15345139
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"