Proinflammatory cytokine expression in cyclooxygenase-2-deficient primary osteoblasts.

Many of the proinflammatory effects of interleukin (IL)-1beta and tumor necrosis factor-alpha (TNF-alpha) are mediated through cyclooxygenase-2 (COX-2)-dependent prostaglandin E2 (PGE2). The purpose of this study was to examine the expression of IL-1beta and TNF-alpha in COX-2-deficient osteoblasts during inflammation. Primary osteoblasts prepared from wild-type (WT) and COX-2 knockout (K/O) mice were exposed to lipopolysaccharide (LPS) and endodontic obturation materials. An enzyme-linked immunosorbent assay was used to measure cytokine levels. LPS treatment led to a significant upregulation in IL-1beta and TNF-alpha levels in both WT and K/O cells. TNF-alpha upregulation in response to LPS was much more pronounced in K/O cells compared with WT cells (p < 0.05). All materials tested except for gutta percha caused an increase in IL-1beta expression. In conclusion, there appears to be a positive feedback regulation between TNF-alpha and COX-2-dependent PGE2 during LPS-induced inflammatory reactions.