The new IL-1 family member IL-1F8 stimulates production of inflammatory mediators by synovial fibroblasts and articular chondrocytes

Six novel members of the IL-1 family of cytokines were recently identified, primarily through the use of DNA database searches for IL-1 homologues, and were named IL-1F5 to IL-1F10. In the present study, we investigated the effect of IL-1F8 on primary human joint cells, and examined the expression of the new IL-1 family members in human and mouse joints. Human synovial fibroblasts (hSFs) and human articular chondrocytes (hACs) expressed the IL-1F8 receptor (IL-1Rrp2) and produced pro-inflammatory mediators in response to recombinant IL-1F8. IL-1F8 mRNA expression was increased in hSFs upon stimulation with proinflammatory cytokines, whereas in hACs IL-1F8 mRNA expression was constitutive. However, IL-1F8 protein was undetectable in hSF and hAC culture supernatants. Furthermore, although IL-1β protein levels were increased in inflamed human and mouse joint tissue, IL-1F8 protein levels were not. IL-1F8 levels in synovial fluids were similar to or lower than those in matched serum samples, suggesting that the joint itself is not a major source of IL-1F8. Serum levels of IL-1F8 were similar in healthy donors, and patients with rheumatoid arthritis, osteoarthritis and septic shock, and did not correlate with inflammatory status. Interestingly however, we observed high IL-1F8 levels in several serum samples in all groups. In conclusion, IL-1F8 exerts proinflammatory effects in primary human joint cells. Joint and serum IL-1F8 protein levels did not correlate with inflammation, but they were high in some human serum samples tested, including samples from patients with rheumatoid arthritis. It remains to be determined whether circulating IL-1F8 can contribute to joint inflammation in rheumatoid arthritis

To test or not to test: A cross-sectional survey of the psychosocial determinants of self-testing for cholesterol, glucose, and HIV

Contains fulltext : 97466.pdf (publisher's version ) (Open Access)BACKGROUND: Although self-tests are increasingly available and widely used, it is not clear whether their use is beneficial to the users, and little is known concerning the determinants of self-test use. The aim of this study was to identify the determinants of self-test use for cholesterol, glucose, and HIV, and to examine whether these are similar across these tests. Self-testing was defined as using in-vitro tests on body materials, initiated by consumers with the aim of diagnosing a particular disorder, condition, or risk factor for disease. METHODS: A cross-sectional Internet survey was conducted among 513 self-testers and 600 non-testers, assessing possible determinants of self-test use. The structured questionnaire was based on the Health Belief Model, Theory of Planned Behavior, and Protection Motivation Theory. Data were analyzed by means of logistic regression. RESULTS: The results revealed that perceived benefits and self-efficacy were significantly associated with self-testing for all three conditions. Other psychosocial determinants, e.g. gender, cues to action, perceived barriers, subjective norm, and moral obligation, seemed to be more test-specific. CONCLUSIONS: Psychosocial determinants of self-testing are not identical for all tests and therefore information about self-testing needs to be tailored to a specific test. The general public should not only be informed about advantages of self-test use but also about the disadvantages. Designers of information about self-testing should address all aspects related to self-testing to stimulate informed decision making which, in turn, will result in more effective self-test use

The mosaic of KIR haplotypes in rhesus macaques

To further refine and improve biomedical research in rhesus macaques, it is necessary to increase our knowledge concerning both the degree of allelic variation (polymorphism) and diversity (gene copy number variation) in the killer cell immunoglobulin-like receptor (KIR) gene cluster. Pedigreed animals in particular should be studied, as segregation data will provide clues to the linkage of particular KIR genes/alleles segregating on a haplotype and to its gene content as well. A dual strategy allowed us to screen the presence and absence of genes and the corresponding transcripts, as well as to track differences in transcription levels. On the basis of this approach, 14 diverse KIR haplotypes have been described. These haplotypes consist of multiple inhibitory and activating Mamu-KIR genes, and any gene present on one haplotype may be absent on another. This suggests that the cost of accelerated evolution by recombination may be the loss of certain framework genes on a haplotype

Male Mating Tactics in Captive Rhesus Macaques (Macaca mulatta): The Influence of Dominance, Markets, and Relationship Quality

Male mating success in a multimale–multifemale group can depend on several variables: body condition, dominance, coalitions, “friendship,” or an exchange of services for mating access. Exchange patterns may also be determined by market effects or social relationships. We studied the mating tactics of males in a captive, multimale–multifemale group of rhesus macaques and the resulting patterns of mating and paternity to determine the influence of dominance rank, mating markets, and relationship quality on their mating tactics. Male rank was positively related to the total number of copulations and the number of mating partners, but did not explain male mating distribution completely. Moreover, male fertilization success was not related to male rank. Males did not exchange grooming for mating access on the same day and neither the supply nor the rank (as a proxy for quality) of receptive females affected the amount of male grooming, suggesting that market effects did not explain male mating access. However, there was a positive correlation between long-term grooming patterns of both males and females and mating access, indicating that social relationships were important for male mating access. Paternity data revealed that these social relationships were also important for male reproductive success. We conclude that both male rank and male–female “friendship” determined male mating access in these rhesus macaques, but that “friendship” was more important in determining paternity, emphasizing the importance of intersex social bonds in male mating success in multimale primate societies

Innate and adaptive immunity to human beta cell lines:implications for beta cell therapy

AIMS/HYPOTHESIS: Genetically engineered human beta cell lines provide a novel source of human beta cells to study metabolism, pharmacology and beta cell replacement therapy. Since the immune system is essentially involved in beta cell destruction in type 1 diabetes and after beta cell transplantation, we investigated the interaction of human beta cell lines with the immune system to resolve their potential for immune intervention protocol studies. METHODS: Human pancreatic beta cell lines (EndoC-βH1 and ECi50) generated by targeted oncogenesis in fetal pancreas were assessed for viability after innate and adaptive immune challenges. Beta cell lines were pre-conditioned with T helper type 1 (Th1) cytokines or high glucose to mimic inflammatory and hyperglycaemia-stressed conditions. Beta cells were then co-cultured with auto- and alloreactive cytotoxic T cells (CTL), natural killer (NK) cells, supernatant fraction from activated autoreactive Th1 cells, or alloantibodies in the presence of complement or effector cells. RESULTS: Low HLA expression protected human beta cell lines from adaptive immune destruction, but it was associated with direct killing by activated NK cells. Autoreactive Th1 cell inflammation, rather than glucose stress, induced increased beta cell apoptosis and upregulation of HLA, increasing beta cell vulnerability to killing by auto- and alloreactive CTL and alloreactive antibodies. CONCLUSIONS/INTERPRETATION: We demonstrate that genetically engineered human beta cell lines can be used in vitro to assess diverse immune responses that may be involved in the pathogenesis of type 1 diabetes in humans and beta cell transplantation, enabling preclinical evaluation of novel immune intervention strategies protecting beta cells from immune destruction. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00125-015-3779-1) contains peer-reviewed but unedited supplementary material, which is available to authorised users