Involvement of RhoA/ROCK signaling for alteration of stress fiber via lymphotoxin β receptor stimulation in fibroblastic reticular cell isolated from lymph node

The heterotrimeric transmembrane lymphotoxin α1β2 (LTα1β2), member of the tumor necrosis factor family cytokines including soluble homotrimeric lymphotoxin α (LTα), plays an important role in lymphoid tissue architecture and organogenesis. We found that lymphotoxin β receptor (LTβR) stimulation using agonistic anti-LTβR antibody induced the changes in actin stress fiber and morphology of cells. To address the possibility that LTβR stimulation is involved in RhoA/Rho-associated protein kinase (ROCK) signaling, we checked the level of Rho-guanosine diphosphate (GDP)/guanosine triphosphate (GTP) exchange activity with fibroblastic reticular cell (FRC) lysate. When LTβR was stimulated with agonistic anti-LTβR antibody, the Rho-GDP/GTP exchange activity was markedly reduced. Inhibition of ROCK activity induced changes in actin cytoskeleton organization and cell morphology in FRC. We showed that the phosphorylation of myosin light chains (MLCs) was reduced by LTβR stimulation in FRC. DNA gene chip demonstrated ...