IL-1β-Induced Mesenchymal Stem Cell Migration Involves MLCK Activation via PKC Signaling.

Mesenchymal stem cells (MSCs) migrate via the bloodstream to sites of injury, possibly attracted by inflammatory cytokines. Although many cytokines can induce stem cell migration, the underlying mechanism is not fully understood. We found that tail vein-injected MSCs migrate to the pancreas in nonobese diabetic (NOD) mice. An ELISA assay revealed that hyperglycemic NOD mice have higher pancreatic levels of interleukin-1β (IL-1β) than normal NOD mice and that IL-1β stimulates MSC migration in a Transwell assay and electric cell–substrate impedance sensing system. Microarray analysis showed that myosin light chain kinase (MLCK) is involved in IL-1β-induced MSC migration, while Western blots showed that IL-1β stimulates MLCK expression and activation and that MLCK-siRNA transfection reduces MSC migration. Kinase inhibitors, chromatin immunoprecipitation, and a knockdown study revealed that IL-1β-induced MLCK expression is regulated by the PKCd/NF-κB signaling pathway, and a kinase inhibitor study revealed th...