Kawasaki disease is a systemic vasculitis of unknown etiology, with clinical observations suggesting a substantial genetic contribution to disease susceptibility. We conducted a genome-wide association study and replication analysis in 2,173 individuals with Kawasaki disease and 9,383 controls from five independent sample collections. Two loci exceeded the formal threshold for genome-wide significance. The first locus is a functional polymorphism in the IgG receptor gene FCGR2A (encoding an H131R substitution) (rs1801274; P = 7.35 × 10(-11), odds ratio (OR) = 1.32), with the A allele (coding for histadine) conferring elevated disease risk. The second locus is at 19q13, (P = 2.51 × 10(-9), OR = 1.42 for the rs2233152 SNP near MIA and RAB4B; P = 1.68 × 10(-12), OR = 1.52 for rs28493229 in ITPKC), which confirms previous findings(1). The involvement of the FCGR2A locus may have implications for understanding immune activation in Kawasaki disease pathogenesis and the mechanism of response to intravenous immunoglobulin, the only proven therapy for this disease.
Background and PurposeAtopic dermatitis (AD) is a multifactorial skin condition with complex interactions of innate and adaptive immune responses. There are several existing therapies for AD, including topical glucocorticosteroids, emollients, phototherapies, calcineurin inhibitors and immunosuppressants, such as cyclosporine A. Although these therapies reduce inflammation, they also cause serious side effects. Therefore, it is necessary to develop new therapeutic approaches for AD treatment without side effects. There are several studies on natural materials or toxins, such as herbs, ginseng extract and snake venom, for AD treatment. However, treatment of AD with bee venom and its major component, melittin has rarely been studied.Experimental ApproachEffects of bee venom and melittin were studied in a model of AD in vivo induced by 1‐chloro‐2,4‐dinitrobenzene (DNCB) in female Balb/c mice and in cultures of human keratinocytes, stimulated by TNF‐α/IFN‐γ. The potential pharmacological effects of bee venom and melittin on these in vivo and in vitro AD‐like skin disease models were studied.Key ResultsBee venom and melittin exhibited potent anti‐atopic activities, shown by decreased AD‐like skin lesions, induced by DNCB in mice. In vitro studies using TNF‐α/IFN‐γ‐stimulated human keratinocytes showed that bee venom and melittin inhibited the increased expression of chemokines, such as CCL17 and CCL22, and pro‐inflammatory cytokines, including IL‐1β, IL‐6 and IFN‐γ, through the blockade of the NF‐κB and STAT signalling pathways.Conclusions and ImplicationsOur results suggest that bee venom and melittin would be suitable for epicutaneous application, as topical administration is often appropriate for the treatment of AD.
OBJECTIVE
To determine whether trophoblast-derived microparticles can induce different inflammatory responses of the peripheral blood mononuclear cells (PBMCs) depending upon the state of trophoblast when the microparticles are generated.
STUDY DESIGN
A trophoblast-derived cell line (ATCC No. CRL-1584) was cultured under normal or hypoxic conditions. Microparticles were isolated from the cell culture supernatants (MP_C: microparticles from normal trophoblast; MP_H: microparticles from hypoxic trophoblast). PBMCs were cultured alone or co-cultured with either MP_C or MP_H.
RESULTS
1) After 48 hours, the PBMCs co-cultured with MP_C released higher concentrations of IL-6 than PBMCs cultured alone; 2) The PBMCs co-cultured with MP_H showed higher concentration of IL-6 and TNF-a than PBMCs co-cultured with PM_C, after 24 hours and 48 hours.
CONCLUSION
More intense and rapid inflammatory response of PBMCs was observed with MP_H than with MP_C. This difference might explain the exaggerated systemic inflammatory response as a result of placental hypoxia in preeclampsia.
Tai Chi was safely implemented as an alternative form of exercise in a cardiovascular risk management programme. Whether the beneficial effects of Tai Chi in cardiovascular risk management are comparable with those induced by other types of aerobic exercise requires further investigation.
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