Goat Anti-Human TNF-alpha polyclonal antibody

Introduction Osteonecrosis of the jaw (ONJ) occurring after invasive dental treatment often adversely affects patients' activities of daily living. Long-term administration of strong anti-bone resorptive agents such as bisphosphonates prior to invasive dental treatment is considered an ONJ risk factor; however, pathological mechanisms underlying ONJ development remain unclear. Materials and Methods We developed an ONJ mouse model in which a tooth is extracted during treatment with the bisphosphonate zoledronate. Results We observed induction of apoptosis in osteocytes, resulting in formation of empty lacunae in jaw bones at sites of tooth extraction but not in other bones of the same mice. We also observed elevated levels of inflammatory cytokines such as TNF alpha, IL-6 and IL-1 in jaw bone at the extraction site relative to other sites in zoledronate-treated mice. We also report that treatment in vitro with either zoledronate or an extract from Porphyromonas gingivalis, an oral bacteria, promotes expression of inflammatory cytokines in osteoclast progenitor cells. We demonstrate that gene-targeting of either TNF alpha, IL-6 or IL-1 or treatment with etanercept, a TNF alpha inhibitor, or a neutralizing antibody against IL-6 can antagonize ONJ development caused by combined tooth extraction and zoledronate treatment. Conclusions Taken together, the cytokine storm induced by invasive dental treatment under bisphosphonate treatment promotes ONJ development due to elevated levels of inflammatory cytokine-producing cells. Our work identifies novel targets potentially useful to prevent ONJ.

Infections are able to trigger epigenetic modifications; however, epigenetic-mediating infections in the immune system in fish is currently unavailable. Within this purpose, zebrafish were immune-stimulated with three lipopolysaccharides (LPS) during sex differentiation. Methylation patterns of three immune genes were studied by a candidate gene approach together with gene expression analysis, and in adulthood, sex ratios were determined. It was shown that the entrance of LPS was through the gills and accumulated in the pronephms. Significant hypomethylation levels of CASP9 and a significant CpG site for IL1 beta after Pseudomonas aeruginosa LPS exposure were found. No methylation difference was observed for TNF alpha. Gene expression and correlation data differed among studied genes. Sex ratios showed a feminization in dose and LPS strain-dependent manner. Here, it is provided epigenetic regulatory mechanisms derived by innate response and the first evidence of possible epigenetic interactions between the immune and reproductive systems.