PMID- 31726048
OWN - NLM
STAT- MEDLINE
DCOM- 20200727
LR  - 20211204
IS  - 1873-2968 (Electronic)
IS  - 0006-2952 (Linking)
VI  - 171
DP  - 2020 Jan
TI  - Janus kinase inhibitor ruxolitinib blocks thymic regeneration after acute thymus 
      injury.
PG  - 113712
LID - S0006-2952(19)30411-3 [pii]
LID - 10.1016/j.bcp.2019.113712 [doi]
AB  - Thymic epithelial cells (TECs) are crucial for the production of T-cells. Cancer 
      therapies including cytotoxic drugs and ionizing radiations damage TECs resulting 
      in abnormal T-cell production and function. Fortunately, TECs can regenerate 
      after injury. The Janus kinase (Jak) pathway is important in supporting survival 
      of TECs. Jak inhibitors are used to treat cancer and immune disorders. The impact 
      of Jak inhibitors on recovery of TECs is unknown. We induced acute thymus injury 
      in mice by using ionizing radiation and evaluated the impact of ruxolitinib on 
      thymus regeneration. We also tested if ruxolitinib affected proliferation of TECs 
      in vitro. An increase was observed in the recovery of thymus cells after acute 
      injury in association with up-regulation of TEC-related growth factors including 
      keratinocyte growth factor (Kgf), epidermal growth factor (Egf), insulin-like 
      growth factor 1 (Igf1) and receptor activator of NF-kappaB ligand (Rankl). Giving 
      ruxolitinib decreased levels of receptors of these growth factors on TECs and 
      blocked growth factor-induced recovery of thymus cells in damaged thymii. 
      Ruxolitinib also blocked growth factors-induced proliferation of TECs in vitro. 
      Thymus regeneration was inhibited when ruxolitinib was given immediately after 
      thymus injury but not when it was given 1 week later. These data may have 
      implications for how ruxolitinib is used in clinical practices.
CI  - Copyright (c) 2019 Elsevier Inc. All rights reserved.
FAU - Li, Lingling
AU  - Li L
AD  - Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China.
FAU - Shang, Longmei
AU  - Shang L
AD  - Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China.
FAU - Gao, Jun
AU  - Gao J
AD  - Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China.
FAU - Liu, Cong
AU  - Liu C
AD  - Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China.
FAU - Xia, Fan
AU  - Xia F
AD  - Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China; Department of 
      Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou Medical 
      University, Xuzhou, China.
FAU - Xu, Mengdi
AU  - Xu M
AD  - Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China; Department of 
      Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou Medical 
      University, Xuzhou, China.
FAU - Qi, Kunming
AU  - Qi K
AD  - Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China; Department of 
      Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou Medical 
      University, Xuzhou, China.
FAU - Zeng, Lingyu
AU  - Zeng L
AD  - Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China; Department of 
      Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou Medical 
      University, Xuzhou, China.
FAU - Pan, Bin
AU  - Pan B
AD  - Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China; Department of 
      Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou Medical 
      University, Xuzhou, China. Electronic address: panb@xzhmu.edu.cn.
FAU - Xu, Kailin
AU  - Xu K
AD  - Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China; Department of 
      Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou Medical 
      University, Xuzhou, China. Electronic address: xukl@xzhmu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191111
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Janus Kinase Inhibitors)
RN  - 0 (Nitriles)
RN  - 0 (Pyrazoles)
RN  - 0 (Pyrimidines)
RN  - 0 (Receptors, Growth Factor)
RN  - 82S8X8XX8H (ruxolitinib)
RN  - EC 2.7.10.2 (Janus Kinases)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Cell Proliferation/*drug effects/radiation effects
MH  - Epithelial Cells/*drug effects/metabolism/radiation effects
MH  - Female
MH  - Intercellular Signaling Peptides and Proteins/metabolism
MH  - Janus Kinase Inhibitors/pharmacology
MH  - Janus Kinases/metabolism
MH  - Mice, Inbred BALB C
MH  - Nitriles
MH  - Pyrazoles/*pharmacology
MH  - Pyrimidines
MH  - Receptors, Growth Factor/metabolism
MH  - Regeneration/*drug effects/radiation effects
MH  - Signal Transduction/drug effects/radiation effects
MH  - T-Lymphocytes/drug effects/metabolism/radiation effects
MH  - Thymus Gland/*drug effects/physiopathology/radiation effects
OTO - NOTNLM
OT  - Jak inhibitor
OT  - Ruxolitinib
OT  - Thymic epithelial cell
OT  - Thymus
EDAT- 2019/11/15 06:00
MHDA- 2020/07/28 06:00
CRDT- 2019/11/15 06:00
PHST- 2019/09/09 00:00 [received]
PHST- 2019/11/08 00:00 [accepted]
PHST- 2019/11/15 06:00 [pubmed]
PHST- 2020/07/28 06:00 [medline]
PHST- 2019/11/15 06:00 [entrez]
AID - S0006-2952(19)30411-3 [pii]
AID - 10.1016/j.bcp.2019.113712 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2020 Jan;171:113712. doi: 10.1016/j.bcp.2019.113712. Epub 2019 
      Nov 11.