Angiotensin II sustains brain inflammation in mice via TGF-beta (J Clin Invest, 2010, 120:2782-2794)

報告日期: 2010/10/12
報告時間: 16:00/16:50
報告學生: 吳佩樺
講評老師: 郭余民

Angiotensin II sustains brain inflammation in mice via TGF-β

J Clin Invest. 2010;120(8):2782–2794


Speaker: Peihua Wu (吳佩樺)

Commentator: Yu-Min Kuo (郭余民)

Time: 16:00-16:50, Oct 12, 2010

Place: Room 602



Multiple sclerosis (MS) is a common neurological disease characterized with inflammation and demyelination in the lesions of the central nervous system (CNS)(1). It is known that blockaded the signals of angiotensin II (Ang II), the major regulator of the renin-angiotensin-aldosterone system, or TGF-β, a multipotent cytokine involved in inflammation and T cell differentiation, ameliorates experimental autoimmune encephalomyelitis (EAE), respectively (2, 3). Here, the authors hypothesized that Ang II may interplay with TGF-β signaling, further contribute to EAE development. They found Ang II type 1 receptor (AT1R) was upregulated mainly on CNS resident cells, such as astrocytes, neurons, and microglial cells, during MOG35-55-induced EAE. Ang II-treated primary cultured microglial cells and astrocytes exhibited TGF-β-activating protease thrombospondin-1 (TSP-1)- dependent TGF-β expression and activation, respectively. In vivo bioluminescence and immunohistochemistry data showed that TGF-β as well as its signaling in the CNS is upregulated Ang II dependently during chronic EAE. Since TSP-1 is the major activator of TGF-β, they found TSP-1 was also markedly increased in the CNS during chronic EAE. This increase was blocked by treatment with the AT1R blocker candesartan (CA). Furthermore, CA-treated or Agtr1-/- mice showed a delayed onset and reduced severity of disease after MOG35-55 immunization. Collectively these results revealed that Ang II induces activation of TGF-β via upregulation of TSP-1 in the CNS during chronic EAE. This study further suggested the potential role of AT1R antagonist for attenuating neuroinflammation in patients with MS.



1   Stadelmann, C., Wegner, C., & Bruck, W., Inflammation, demyelination, and degeneration - Recent insights from MS pathology. Biochim Biophys Acta.

2   Luo, J. et al., Glia-dependent TGF-beta signaling, acting independently of the TH17 pathway, is critical for initiation of murine autoimmune encephalomyelitis. J Clin Invest 117 (11), 3306-3315 (2007).

3   Platten, M. et al., Blocking angiotensin-converting enzyme induces potent regulatory T cells and modulates TH1- and TH17-mediated autoimmunity. Proc Natl Acad Sci U S A 106 (35), 14948-14953 (2009).