Format

Send to

Choose Destination
Immunol Lett. 2018 Nov;203:62-69. doi: 10.1016/j.imlet.2018.09.012. Epub 2018 Sep 18.

Cucurbitacin E ameliorates acute graft-versus-host disease by modulating Th17 cell subsets and inhibiting STAT3 activation.

Author information

1
The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, College of Medicine, Seoul, South Korea.
2
Division of Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
3
The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, College of Medicine, Seoul, South Korea; Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, South Korea. Electronic address: iammila@catholic.ac.kr.

Abstract

Cucurbitacin E (CuE) is a biochemical compound found in plants that are members of the family CuE has been studied for its roles in anti-inflammation and the inhibition of angiogenesis as well as for its properties as an antioxidant. CuE is a new agent that was identified as a selective inhibitor of the signal transducer and activator of transcription 3 (STAT3)-related pathway. STAT3, a pivotal transcription factor for Th17 differentiation, is critical for T cell alloactivation in acute graft-versus-host disease (aGvHD). We investigated whether CuE attenuates the development of aGvHD through the suppression of Th17 cells. The alloreactive proliferation of mouse and human T cells was reduced by CuE treatment. CuE also decreased pro-inflammatory cytokines, such as IL-17 and IFN-γ, in alloreactive T cells. STAT3-responsive and IL-17A-promoter activities were also suppressed by CuE treatment, confirming that activated STAT3 was decreased by CuE treatment. To construct an aGvHD-induced mouse line, splenocytes and bone marrow cells from C57BL/6 mice were transplanted into BALB/c mice with complete mis-matched major histocompatibility complex molecules. CuE was administered to aGvHD animals 3 days per week via intraperitoneal injection. CuE attenuated the severity of aGvHD disease-related scores compared to the vehicle group. CuE inhibited skin inflammation and fibrosis, as evidenced by the expression of α-Sma and Col-I in aGvHD mice compared to the vehicle group. Additionally, aGvHD mice treated with CuE showed improved histopathological features in the small and large intestines, whereas the vehicle group showed collapsed villi in the small intestine and cryptic structures in the large intestine. We also observed a marked reduction of pro-inflammatory cytokines in the intestinal tissue. Collectively, our data suggest that CuE could serve as a therapeutic agent for patients with aGvHD.

KEYWORDS:

Acute graft-versus-host disease; Cucurbitacin E; Fibrosis; STAT3; Th17 cells

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center