Lipoteichoic Acid Up-regulates VEGF Expression in Macrophages and Pulp Cells

Vascular endothelial growth factor (VEGF) is a potent inducer of angiogenesis, vascular permeability, and edema. Up-regulation of VEGF expression in the dental pulp may result in increased intra-pulpal pressure, and contribute to pain and irreversible tissue damage. Lipoteichoic acid (LTA) is an amphiphilic molecule from Gram-positive bacteria that has been associated with the pathogenesis of pulpitis. To investigate if LTA regulates expression of VEGF, we exposed mouse odontoblast-like cells (MDPC-23), undifferentiated pulp cells (OD-21), fibroblasts, or macrophages to streptococcal LTA, and evaluated VEGF expression by ELISA and RT-PCR. LTA induced up to a nine-fold increase in VEGF protein expression in macrophages, a 2.4-fold increase in MDPC-23, and a 1.6-fold increase in OD-21 as compared with controls. In contrast, LTA did not induce VEGF expression in fibroblasts. VEGF mRNA expression remained constant upon exposure to LTA, which suggests that VEGF regulation in these cells is primarily post-transcriptional. This work constitutes the first demonstration that lipoteichoic acid is sufficient to induce expression of a pro-angiogenic factor.