Identification of a Lysosomal Pathway That Modulates Glucocorticoid Signaling and the Inflammatory Response

by Yuanzheng He, Yong Xu, Chenghai Zhang, Xiang Gao, Karl J. Dykema, Katie R. Martin, Jiyuan Ke, Eric A. Hudson, Sok Kean Khoo, James H. Resau, Arthur S.

Alberts, Jeffrey P. MacKeigan, Kyle A. Furge, and H. Eric Xu

Sci. Signal.Volume 4(180):ra44-ra44

July 5, 2011

©2011 by American Association for the Advancement of Science

The anti-inflammatory effect of CQ was partially mediated by GR. (A) In THP-1 cells exposed to LPS (1 μg/ml), CQ (50 μM) reduced the mRNA abundance of IL-1β and IL-6 (measured by real-

time PCR) compared to PBS (vehicle)–treated cells exposed to LPS

Yuanzheng He et al., Sci. Signal. 2011;4:ra44

©2011 by American Association for the Advancement of Science

CQ enhances glucocorticoid-mediated GR signaling.

Yuanzheng He et al., Sci. Signal. 2011;4:ra44

©2011 by American Association for the Advancement of Science

Gene expression profiling of THP-1 cells exposed to CQ, Dex, or both.

Yuanzheng He et al., Sci. Signal. 2011;4:ra44

©2011 by American Association for the Advancement of Science

The V-ATPase inhibitor bafilomycin A1 potentiated glucocorticoid signaling by inhibiting lysosomal function.

Yuanzheng He et al., Sci. Signal. 2011;4:ra44

©2011 by American Association for the Advancement of Science

Lysosomal biogenesis master regulator TFEB regulates GR activity.

Yuanzheng He et al., Sci. Signal. 2011;4:ra44

©2011 by American Association for the Advancement of Science

Lysosomes regulate AR and ER activity.

Yuanzheng He et al., Sci. Signal. 2011;4:ra44

©2011 by American Association for the Advancement of Science

A lysosomal pathway contributes to degradation of cytoplasmic GR. (A) Pulse-chase assay of unliganded GR in AD293 cells.

Yuanzheng He et al., Sci. Signal. 2011;4:ra44

©2011 by American Association for the Advancement of Science