Targeted Rho-associated kinase 2 inhibition suppresses murine and human chronic GVHD through a Stat3-dependent mechanism

• Published in: Blood Vol. 127; no. 17; pp. 2144 - 2154
• Main Authors: Flynn, Ryan, Paz, Katelyn, Du, Jing, Reichenbach, Dawn K., Taylor, Patricia A., Panoskaltsis-Mortari, Angela, Vulic, Ante, Luznik, Leo, MacDonald, Kelli K.P., Hill, Geoffrey R., Nyuydzefe, Melanie S., Weiss, Jonathan M., Chen, Wei, Trzeciak, Alissa, Serody, Jon S., Aguilar, Ethan G., Murphy, William J., Maillard, Ivan, Munn, David, Koreth, John, Cutler, Corey S., Antin, Joseph H., Ritz, Jerome, Waksal, Samuel D., Zanin-Zhorov, Alexandra, Blazar, Bruce R.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 28.04.2016; American Society of Hematology
• Subjects: Animals; Bronchiolitis Obliterans - drug therapy; Bronchiolitis Obliterans - etiology; Bronchiolitis Obliterans - physiopathology; Chronic Disease; Cytokines - biosynthesis; Cytokines - genetics; Drug Evaluation, Preclinical; Graft vs Host Disease - drug therapy; Graft vs Host Disease - enzymology; Humans; Leukocytes, Mononuclear - metabolism; Lung - physiopathology; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Molecular Targeted Therapy; Nuclear Receptor Subfamily 1, Group F, Member 3 - biosynthesis; Nuclear Receptor Subfamily 1, Group F, Member 3 - genetics; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; Protein Processing, Post-Translational - drug effects; Proto-Oncogene Proteins c-bcl-6 - biosynthesis; Proto-Oncogene Proteins c-bcl-6 - genetics; rho-Associated Kinases - antagonists & inhibitors; rho-Associated Kinases - physiology; Specific Pathogen-Free Organisms; Spleen - pathology; STAT3 Transcription Factor - deficiency; STAT3 Transcription Factor - physiology; T-Lymphocyte Subsets - drug effects; T-Lymphocyte Subsets - pathology; T-Lymphocyte Subsets - transplantation; Transplantation

Chronic graft-versus-host disease (cGVHD) remains a major complication following allogeneic bone marrow transplantation (BMT). The discovery of novel therapeutics is dependent on assessment in preclinical murine models of cGVHD. Rho-associated kinase 2 (ROCK2) recently was shown to be implicated in...