Activation of the selenopritein SEPS1 gene expression by pro-inflammatory cytokines in Hep G2 cells

SEPS1 (also called selenoprotein S, SelS) plays an important role in the production of inflammatory cytokines and its expression is activated by endoplasmic reticulum (ER) stress. In this report, we have identified two binding sites for the nuclear factor kappa B in the human SEPS1 promoter. SEPS1 gene expression, protein levels and promoter activity were all increased 2–3-fold by TNF-α and IL-1β in HepG2 cells. We have also confirmed that the previously proposed ER stress response element GGATTTCTCCCCCGCCACG in the SEPS1 proximate promoter is fully functional and responsive to ER stress. However, concurrent treatment of HepG2 cells with IL-1β and ER stress produced no additive effect on SEPS1 gene expression. We conclude that SEPS1 is a new target gene of NF-κB. Together with our previous findings that SEPS1 may regulate cytokine production in macrophage cells, we propose a regulatory loop between cytokines and SEPS1 that plays a key role in control of the inflammatory response.

Low dose supplementation with two different marine oils does not reduce pro-inflammatory eicosanoids and cytokines in vivo

In view of the reported potential anti-inflammatory activity of the New Zealand green lipped mussel (NZGLM), we aimed to compare the effect of low dose marine oil supplementation, from mussels and fish, in reducing blood markers of inflammation. Thirty apparently healthy males and females were recruited from the general public in Melbourne, Australia to participate in a double blind, randomised, parallel intervention study. Subjects were consuming approximately 73 mg of omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) daily in their background diet prior to the commencement of the intervention. Subjects were randomly assigned to consume either 2 mL/day of the NZGLM oil preparation (mixed with olive oil and dl-alpha-tocopherol) or fish oil preparation (also mixed with olive oil and dl-alpha-tocopherol) for six weeks. Two mL of the oils contained 241 mg and 181 mg of n-3 LCPUFA, respectively. Neutrophil phospholipid fatty acids, serum thromboxane B2 (TXB2), stimulated monocyte production of prostaglandin E2 (PGE2), interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNFalpha) were measured. During the intervention, the total intakes of n-3 LCPUFA from the background diet and the supplements were 199 mg/d and 173 mg/day for the NZGLM and FO groups, respectively. Following six weeks of supplementation, both groups showed a small, but significant increase in neutrophil phospholipid proportion of eicosapentaenoic acid. The NZGLM group also showed a significant increase in docosahexaenoic acid levels. There were no significant changes with time or treatment for TXB2, PGE2, IL-1 beta or TNFalpha. This study showed that low dose supplementation with n-3 LCPUFA from two different marine oil preparations showed no difference in inflammatory markers in this group of healthy individuals. Further studies are warranted including dose response trials and studies in populations with inflammatory conditions.

St. Johns wort attenuates irinotecan-induced diarhea via down-regulation of intestinal pro-inflammatory cytokines and inhibition of intestinal epithelial apoptosis

Diarrhea is a common dose-limiting toxicity associated with cancer chemotherapy, in particular for drugs such as irinotecan (CPT-11), 5-fluouracil, oxaliplatin, capecitabine and raltitrexed. St. John's wort (Hypericum perforatum, SJW) has anti-inflammatory activity, and our preliminary study in the rat and a pilot study in cancer patients found that treatment of SJW alleviated irinotecan-induced diarrhea. In the present study, we investigated whether SJW modulated various pro-inflammatory cytokines including interleukins (IL-1β, IL-2, IL-6), interferon (IFN-γ) and tumor necrosis factor-α (TNF-α) and intestinal epithelium apoptosis in rats. The rats were treated with irinotecan at 60 mg/kg for 4 days in combination with oral SJW or SJW-free control vehicle at 400 mg/kg for 8 days. Diarrhea, tissue damage, body weight loss, various cytokines including IL-1β, IL-2, IL-6, IFN-γ and TNF-α and intestinal epithelial apoptosis were monitored over 11 days. Our studies demonstrated that combined SJW markedly reduced CPT-11-induced diarrhea and intestinal lesions. The production of pro-inflammatory cytokines such as IL-1β, IFN-γ and TNF-α was significantly up-regulated in intestine. In the mean time, combined SJW significantly suppressed the intestinal epithelial apoptosis induced by CPT-11 over days 5–11. In particular, combination of SJW significantly inhibited the expression of TNF-α mRNA in the intestine over days 5–11. In conclusion, inhibition of pro-inflammatory cytokines and intestinal epithelium apoptosis partly explained the protective effect of SJW against the intestinal toxicities induced by irinotecan. Further studies are warranted to explore the potential for STW as an agent in combination with chemotherapeutic drugs to lower their dose-limiting toxicities.

The relationship between environmental activism, pro-environmental behaviour and social identity

Research on environmental activism remains poorly integrated and ill-defined and to date, there has been little examination of the relationship of environmental activism, pro-environmental behaviour and social identity. 131 students from an Australian University (M = 25.04 years old, SD = 8.17) voluntarily participated by returning an anonymous questionnaire containing an environmental activism scale, a pro-environmental behaviour scale and a social identity scale. The results revealed that while there was a significant relationship between social identity and environmental behaviour, only the citizenship component of environmental behaviour significantly predicted environmental activism. In other words, the relationship between social identity and environmental activism was indirect. This research presents the opportunity for further exploration of these relationships and to further investigate their relationship to inter-group processes.

Legal bans on pro-suicide web sites : an early retrospective from Australia

There are worldwide concerns that pro-suicide web sites may trigger suicidal behaviors among vulnerable individuals. In 2006, Australia became the first country to criminalize such sites, sparking heated debate. Concerns were expressed that the law casts the criminal net too widely; inappropriately interferes with the autonomy of those who wish to die; and has jurisdictional limitations, with off-shore web sites remaining largely immune. Conversely, proponents point out that the law may limit access to domestic pro-suicide web sites, raise awareness of Internet-related suicide, mobilize community efforts to combat it, and serve as a powerful expression of societal norms about the promotion of suicidal behavior.

Effects of parental perception of neighbourhood deprivation and family environment characteristics on pro-social behaviours among 4-12 year old children

Objective : To assess the effect family environment stressors (e.g. poor family functioning and parental psychological distress) and neighbourhood environment on child prosocial behaviour (CPB) and child difficulty behaviour (CDB) among 4-to-12 year old children.

Methods : Analysis of the 2006 Victorian Child Health and Wellbeing Survey (VCHWS) dataset derived from a statewide cross-sectional telephone survey, with a final total sample of 3,370 children.

Results : Only family functioning, parental psychological distress, child gender, and age were associated with CPB, explaining a total of 8% of the variance. Children from healthily functioning families and of parents without any psychological distress exhibited greater prosocial behaviours than those from poorly functioning families and of parents with mental health problems. Neighbourhood environment was not found to contribute to CPB. A total of eight variables were found to predict CDB, explaining a total of 16% of the variance. Poor family and parental psychological functioning as well as poor access to public facilities in the neighbourhood were associated with conduct problems in children.

Conclusion : Our results point to the importance of the family environment in providing a context that fosters the development of empathic, caring and responsible children; and in buffering children in exhibiting behaviour difficulties during the formative years of life. Programs aimed at promoting prosocial behaviours in children need to target stressors on the family environment.