Sensory neurons in the periodontal ligament （PDL） transmit the impulses, which are generated by the mechanical stimulation of the tooth, into the trigeminal ganglion, resulting in the excitement of the nucleus ventralis posteromedialis of the thalamus. When sensory neurons are injured, the neurites become atrophied and degenerated. Nerve growth factor （NGF） belonging to neurotrophic factors plays important roles in neurite extension and regeneration of injured sensory neurons. We evaluated how the major component of the outer membrane of gram-negative bacteria, lipopolysaccharide （LPS）, affected transforming growth factor-beta1 （TGF- β1）-induced NGF expression in rat PDL-derived fibroblasts SCDC2 cells. qRT-PCR and ELISA analyses showed that LPS suppressed TGF- β1-induced NGF synthesis through the activation of Toll-like receptor 4 （TLR4）. In addition, inhibitor of κB （I- κB） kinase-2 （IKK-2） inhibitor, TPCA-1, abrogated LPSinduced suppression of TGF- β1-promoted NGF expression. Intriguingly, western blotting showed that LPS inhibited TGF- β1-induced activation of p38 mitogen-activated protein kinase （MAPK） that mediated TGF- β1-induced intra-cellular signal transduction for NGF expression. These results suggested that TLR4-mediated signaling activated by LPS suppresses TGF- β1-induced NGF expression in PDL fibroblasts by inhibiting TGF- β1-induced p38 MAPK activation in a nuclear factor- κ B-dependent manner, possibly resulting in the suppression of the regeneration of injured PDL neurons.