Effect of Interleukin‐1β on Transforming Growth Factor‐Beta and Bone Morphogenetic Protein‐2 Expression in Human Periodontal Ligament and Alveolar Bone Cells in Culture: Modulation by Avocado and Soybean Unsaponifiables

Abstract

In periodontal disease, interleukin-1beta (IL-1beta) is responsible for the matrix breakdown through excessive production of degrading enzymes by periodontal ligament fibroblasts and osteoblasts. Transforming growth factor-beta (TGF-beta) plays an important role in tissue regeneration as one of the factors capable of counteracting IL-1beta effects. In this study, we investigated the in vitro effect of avocado and soya unsaponifiables (ASU) on the expression of TGF-beta1, TGF-beta2, and bone morphogenetic protein-2 (BMP-2) by human periodontal ligament (HPL) and human alveolar bone (HAB) cells in the presence of IL-1beta. HPL and HAB cells were incubated for 48 hours with ASU (10 microg/ml) in the presence or absence of IL-1beta (10 ng/ml). The steady-state levels of TGF-beta1, TGF-beta2, and BMP-2 mRNAs were determined by Northern blot or reverse transcription-polymerase chain reaction (RT-PCR). The amounts of TGF-beta1 and TGF-beta2 proteins were measured by enzyme-linked immunosorbent assay (ELISA). The data indicated that IL-1beta strongly decreases the expression of TGF-beta1 and TGF-beta2 by HPL cells. ASU were capable of opposing the cytokine effect. In HAB cells, TGF-beta1 and BMP-2 mRNA levels were downregulated by the cytokine. ASU were found to reverse the IL-1beta-inhibiting effect. In contrast, the cytokine stimulated the production of TGF-beta2 in alveolar bone cells, with no significant effect of ASU. The results indicate that the IL-1beta-driven erosive effect in periodontitis could be enhanced by a decreased expression of members of the TGF-beta family. The ASU stimulation of TGF-beta1, TGF-beta2, and BMP-2 expression may explain their promoting effects in the treatment of periodontal disorders, at least partly. These findings support the hypothesis that ASU could exert a preventive action on the deleterious effects exerted by IL-1beta in periodontal diseases.