LIGHT is a member of the tumor necrosis factor (TNF) superfamily, which binds two known receptors, lymphotoxin-beta receptor (LT betaR) and the herpesvirus entry mediator (HVEM)/TR2. We investigated the effects of LIGHT on the human rhabdmyosarcoma cell line RD. LIGHT delayed cell proliferation and induced morphological changes of the cells. These effects were not shown by other TNT family ligands such as TNF alpha and LT alpha, which induced the transcriptional activity of nuclear factor-kappaB (NF-kappaB) and NF-kappaB-responsible chemokine productions in the same manner as did LIGHT. LT alpha1 beta2, another TNF family ligand for LT betaR, was shown to have similar activities in RD cells as LIGHT. Both LIGHT and LT alpha1 beta2 induced the expression of muscle-specific genes such as smooth muscle (SM) alpha -actin, while TNF alpha and LT alpha did not. These findings indicate that LIGHT may be a novel inducer of RD cell differentiation associated with SM alpha -actin expression through the LT betaR.