J Cell Physiol 2012,
PMID: 21437904
Chung, Su Wol; Kwon, Min-Young; Kang, Young-Ho; Chung, Hun-Taeg; Lee, Seon-Jin; Kim, Hong Pyo; Perrella, Mark A
Heme oxygenase (HO)-1 is a cytoprotective molecule that is induced during the response to injury. An increase in HO-1 is an acute indicator of inflammation, and early induction of HO-1 has been suggested to correlate with severity of injury. While a great deal is known about the induction of HO-1 by inflammatory mediators and bacterial lipopolysaccharide (LPS), much less is known about the effects of anti-inflammatory mediators on HO-1 expression. Transforming growth factor (TGF)-β is known to play a critical role in suppressing the immune response, and the TGF-β1 isoform is expressed in inflammatory cells. Thus, we wanted to investigate whether TGF-β1 could inhibit the expression of HO-1 during exposure to an inflammatory stimulus in macrophages. Here we demonstrate that TGF-β1 is able to downregulate LPS-induced HO-1 in mouse macrophages, and this reduction in HO-1 occurred through signaling of TGF-β1 via its type I receptor, and activation of Smad2. This TGF-β1 response is dependent on an intact Ets-binding site (EBS) located 93 base pairs upstream from the mouse HO-1 transcription start site. This EBS is known to be important for Ets-2 transactivation of HO-1 by LPS stimulation, and we show that TGF-β1 is able to suppress LPS-induced Ets-2 mRNA and protein levels in macrophages. Moreover, silencing of Smad2 is able to prevent the suppression of both HO-1 and Ets-2 by TGF-β1 during exposure to LPS. These data suggest that the return of HO-1 to basal levels during the resolution of an inflammatory response may involve its downregulation by anti-inflammatory mediators.
Diseases/Pathways annotated by Medline MESH: Inflammation
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Text Mining Data
heme oxygenase-1 ⊣ Smad2: "
Transforming growth factor-ß1 suppression of endotoxin induced
heme oxygenase-1 in macrophages
involves activation of
Smad2 and downregulation of Ets-2
"
heme oxygenase-1 → Ets-2: "
Transforming growth factor-ß1 suppression of endotoxin induced heme oxygenase-1 in macrophages involves activation of Smad2 and downregulation of Ets-2
"
HO-1 → lipopolysaccharide (LPS): "
While a great deal is known about the induction of HO-1 by inflammatory mediators and bacterial lipopolysaccharide (LPS) , much less is known about the effects of anti-inflammatory mediators on HO-1 expression
"
HO-1 → LPS: "
Here we demonstrate that TGF-ß1 is able to downregulate LPS induced HO-1 in mouse macrophages, and this reduction in HO-1 occurred through signaling of TGF-ß1 via its type I receptor, and activation of Smad2
"
Ets-2 → LPS: "
This EBS is known to be important for Ets-2 transactivation of HO-1 by LPS stimulation, and we show that TGF-ß1 is able to suppress LPS induced Ets-2 mRNA and protein levels in macrophages
"
Manually curated Databases
No curated data.