Rat IP-10 (Colorimetric) ELISA Kit

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious complication associated with bisphosphonate treatment. Zoledronic acid (7,A) is a commonly used bisphosphonate due to its effectiveness in increasing bone density and reducing skeletal events, with evidence that it alters angiogenesis. Replacement of the mevalonate pathway using geranylgeraniol (GGOH) was studied to determine the effects of ZA on angiogenic gene expression in primary human osteoclasts. Osteoclast cultures were generated from peripheral blood mononuclear cells of three patients using the peripheral blood mononuclear cell isolation. These cells were phenotyped by phase-contrast microscopy, tartrate-resistant acid phosphatase staining, and pit assays. Primary osteoclasts were found to express a number of key angiogenic molecules at very high levels. Gene expression levels for 84 human angiogenic factors were determined using PCR arrays. Three genes with significant fold regulation (FR) in response to ZA were as follows: tumor necrosis factor (FR = +2.57, P = 0.050), CXCL9 (FR = +39.48, P = 0.028), and CXCL 10 (FR = +18.52, P = 0.0009). The co-addition of geranylgeraniol with 7,A resulted in the significant down-regulation of these three genes along with CCL2, TGFBR1, ENG, and CXCL1. GGOH reversed the gene changes induced by ZA and may offer a promising treatment for BRONJ.

Respiratory syncytial virus (RSV) is increasingly recognized for causing severe morbidity and mortality in older adults, but there are few studies on the RSV-induced immune response in this population. Information on the immunological processes at play during RSV infection in specific risk groups is essential for the rational and targeted design of novel vaccines and therapeutics. Here, we assessed the antibody and local cytokine response to RSV infection in community-dwelling older adults (>= 60 years of age). During three winters, serum and nasopharyngeal swab samples were collected from study participants during acute respiratory infection and recovery. RSV IgG enzyme-linked immunosorbent assays (ELISA) and virus neutralization assays were performed on serum samples from RSV-infected individuals (n = 41) and controls (n = 563 and n = 197, respectively). Nasal RSV IgA and cytokine concentrations were determined using multiplex immunoassays in a subset of participants. An in vitro model of differentiated primary bronchial epithelial cells was used to assess RSV-induced cytokine responses over time. A statistically significant increase in serum neutralization titers and IgG concentrations was observed in RSV-infected participants compared to controls. During acute RSV infection, a statistically significant local upregulation of beta interferon (IFN-beta), IFN-lambda 1, IFN-gamma, interleukin 1 beta (IL-1 beta), tumor necrosis factor alpha (TNF-alpha), IL-6, IL-10, CXCL8, and CXCL10 was found. IFN-beta, IFN-lambda 1, CXCL8, and CXCL10 were also upregulated in the epithelial model upon RSV infection. In conclusion, this study provides novel insights into the basic immune response to RSV infection in an important and understudied risk population, providing leads for future studies that are essential for the prevention and treatment of severe RSV disease in older adults. IMPORTANCE Respiratory syncytial virus (RSV) can cause severe morbidity and mortality in certain risk groups, especially infants and older adults. Currently no (prophylactic) treatment is available, except for a partially effective yet highly expensive monoclonal antibody. RSV therefore remains a major public health concern. To allow targeted development of novel vaccines and therapeutics, it is of great importance to understand the immunological mechanisms that underlie (protection from) severe disease in specific risk populations. Since most RSV-related studies focus on infants, there are only very limited data available concerning the response to RSV in the elderly population. Therefore, in this study, RSV-induced antibody responses and local cytokine secretion were assessed in community-dwelling older adults. These data provide novel insights that will benefit ongoing efforts to design safe and effective prevention and treatment strategies for RSV in an understudied risk group.