scholarly journals Leukemia Inhibitory Factor Induces the Chemomigration of Immortalized Gonadotropin-Releasing Hormone Neurons through the Independent Activation of the Janus Kinase/Signal Transducer and Activator of Transcription 3, Mitogen-Activated Protein Kinase/Extracellularly Regulated Kinase 1/2, and Phosphatidylinositol 3-Kinase/Akt Signaling Pathways

2007 ◽  
Vol 21 (5) ◽  
pp. 1163-1174 ◽  
Author(s):  
Paolo Magni ◽  
Elena Dozio ◽  
Massimiliano Ruscica ◽  
Hajime Watanobe ◽  
Anna Cariboni ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Leukemia Inhibitory Factor ◽  
Akt Signaling ◽  
Gonadotropin Releasing Hormone ◽  
Janus Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Signal Transducer ◽  
Phosphatidylinositol 3 Kinase ◽  
Mitogen Activated Protein ◽  
Transcription 3

scholarly journals Borrelia burgdorferi-Induced Expression of Matrix Metalloproteinases from Human Chondrocytes Requires Mitogen-Activated Protein Kinase and Janus Kinase/Signal Transducer and Activator of Transcription Signaling Pathways

2004 ◽  
Vol 72 (5) ◽  
pp. 2864-2871 ◽  
Author(s):  
Aruna K. Behera ◽  
Cheleste M. Thorpe ◽  
J. Michael Kidder ◽  
Wendy Smith ◽  
Ethan Hildebrand ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Janus Kinase ◽  
Lyme Arthritis ◽  
Mitogen Activated Protein Kinase ◽  
Cartilage Explants ◽  
Human Chondrocytes ◽  
Signal Transducer ◽  
Tnf Α ◽  
Mitogen Activated Protein ◽  
Infected Cells

ABSTRACT Elevations in matrix metalloproteinase 1 (MMP-1) and MMP-3 have been found in patients with Lyme arthritis and in in vitro models of Lyme arthritis using cartilage explants and chondrocytes. The pathways by which B. burgdorferi, the causative agent of Lyme disease, induces the production of MMP-1 and MMP-3 have not been elucidated. We examined the role of the extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK) and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways in MMP induction by B. burgdorferi. Infection with B. burgdorferi results in rapid phosphorylation of p38 and JNK within 15 to 30 min. Inhibition of JNK and p38 MAPK significantly reduced B. burgdorferi-induced MMP-1 and MMP-3 expression. Inhibition of ERK1/2 completely inhibited the expression of MMP-3 in human chondrocytes following B. burgdorferi infection but had little effect on the expression of MMP-1. B. burgdorferi infection also induced phosphorylation and nuclear translocation of STAT-3 and STAT-6 in primary human chondrocytes. Expression of MMP-1 and MMP-3 was significantly inhibited by inhibition of JAK3 activity. Induction of MMP-1 and -3 following MAPK and JAK/STAT activation was cycloheximide sensitive, suggesting synthesis of intermediary proteins is required. Inhibition of tumor necrosis factor alpha (TNF-α) significantly reduced MMP-1 but not MMP-3 expression from B. burgdorferi-infected cells; inhibition of interleukin-1β (IL-1β) had no effect. Treatment of B. burgdorferi-infected cells with JAK and MAPK inhibitors significantly inhibited TNF-α induction, consistent with at least a partial role for TNF-α in B. burgdorferi-induced MMP-1 expression in chondrocytes.

Sign in / Sign up

Export Citation Format

Share Document