MAI Yuxin, WANG Luoziyi, YU Peng, et al. TO90 inhibits angiotensin Ⅱ-induced inflammatory response by up-regulating ACE2/Ang-(1-7)/MAS receptor axis in human retinal pigment epithelial cells. [J]. Journal of Army Medical University 41(20):1932-1938(2019)
MAI Yuxin, WANG Luoziyi, YU Peng, et al. TO90 inhibits angiotensin Ⅱ-induced inflammatory response by up-regulating ACE2/Ang-(1-7)/MAS receptor axis in human retinal pigment epithelial cells. [J]. Journal of Army Medical University 41(20):1932-1938(2019) DOI: 10.16016/j.1000-5404.201905190.
TO90 inhibits angiotensin Ⅱ-induced inflammatory response by up-regulating ACE2/Ang-(1-7)/MAS receptor axis in human retinal pigment epithelial cells
Objective To investigate whether TO90 inhibits angiotensin Ⅱ(Ang Ⅱ)-induced inflammatory response by regulating the expressions of ACE2/Ang-(1-7)/MAS receptor axis in human retinal pigment epithelial cells. Methods In vitro cultured ARPE-19 cells were treated with Ang Ⅱ for 48 h
and the changes in the expressions of interleukin-6(IL-6)
IL-8 and monocyte chemoattractant protein-1(MCP-1) were detected using real-time PCR and enzyme-linked immunosorbent assay(ELISA) to verify the establishment of the inflammatory cell model. The effect of TO90 on the inflammatory response of Ang Ⅱ-treated ARPE-19 cells was evaluated by detecting the expression of IL-6
IL-8
MCP-1
ACE2 and MAS receptor using real-time PCR and Western blotting. ARPE-19 cells treated with Ang Ⅱ
TO90+Ang Ⅱ
A779(a MAS receptor inhibitor)+TO90+Ang Ⅱ
or A779+Ang Ⅱ were examined for expressions of IL-6
IL-8
MCP-1
ACE2 and MAS receptors to further explore the effect of TO90 on Ang Ⅱ-induced inflammation response. Results Ang Ⅱ treatment resulted in significantly increased expressions of IL-6
IL-8 and MCP-1 at both the mRNA and protein levels in ARPE-19 cells(P<0.05)
and these effects were obviously attenuated by pretreatment of the cells with TO90(P<0.05)
which also caused significantly increased expressions of ACE2 and MAS receptor in the cells(P<0.05). In ARPE-19 cells treated with TO90+Ang Ⅱ
inhibition of MAS receptor with A779 significantly enhanced the expression of IL-6
IL-8
MCP-1
while inhibited the expression of ACE2 and MAS receptor at both the mRNA and protein levels(P<0.05). Conclusion TO90 inhibits Ang Ⅱ-induced inflammatory response by up-regulating the expressions of ACE2/Ang-(1-7)/MAS receptor axis in ARPE-19 cells.