Abstract
The TGF-β (transforming growth factor-β) pathway represents an important signalling pathway involved in regulating diverse biological processes, including cell proliferation, differentiation and inflammation. Despite the critical role for TGF-β in inflammatory responses, its role in regulating NF-κB (nuclear factor-κB)-dependent inflammatory responses still remains unknown. In the present study we show that TGF-β1 synergizes with proinflammatory cytokine TNF-α (tumour necrosis factor-α) to induce NF-κB activation and the resultant inflammatory response in vitro and in vivo. TGF-β1 synergistically enhances TNF-α-induced NF-κB DNA binding activity via induction of RelA acetylation. Moreover, synergistic enhancement of TNF-α-induced RelA acetylation and DNA-binding activity by TGF-β1 is mediated by PKA (protein kinase A). Thus the present study reveals a novel role for TGF-β in inflammatory responses and provides new insight into the regulation of NF-κB by TGF-β signalling.
Original language | English |
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Pages (from-to) | 583-591 |
Number of pages | 9 |
Journal | Biochemical Journal |
Volume | 417 |
Issue number | 2 |
DOIs | |
State | Published - 15 Jan 2009 |
Keywords
- Inflammatory response
- Nuclear factor-κB (NF-κB)
- Protein kinase A (PKA)
- RelA acetylation
- Transforming growthfactor-β1 (TGF-β1)
- Tumour necrosis factor-α (TNF-α)