作者机构：
[Yu, Xiaohua; Zhao, Guojun; Yin, Kai; Li, Xiaoxu; Tang, Chaoke; Jiang, Zhisheng; Xiao, Ji; Mo, Zhongcheng] Univ S China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Life Sci Res Ctr, Hengyang 421001, Peoples R China.;[Yu, Xiaohua] Univ S China, Sch Nursing, Hengyang 421001, Peoples R China.;[Fu, Yuchang] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA.;[Zha, Xiaohui] Univ Ottawa, Ottawa Hosp, Res Inst, Ottawa, ON K1H 8L6, Canada.
通讯机构：
[Tang, Chaoke] U;Univ S China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Life Sci Res Ctr, Hengyang 421001, Peoples R China.
关键词：
Niemann–Pick type C1;oxLDL;ERK1/2;COX-2;PPARα;cholesterol
摘要：
The Niemann–Pick type C1 (NPC1) is located mainly in the membranes of the late endosome/lysosome and controls the intracellular cholesterol trafficking from the late endosome/lysosome to the plasma membrane. It has been reported that oxidized low-density lipoprotein (oxLDL) can up-regulate NPC1 expression. However, the detailed mechanisms are not fully understood. In this study, we investigated the effect of oxLDL stimulation on NPC1 expression in THP-1 macrophages. Our results showed that oxLDL up-regulated NPC1 expression at both mRNA and protein levels in a dose-dependent and time-dependent manner. In addition, oxLDL also induced the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). Treatment with oxLDL significantly increased cyclooxygenase-2 (COX-2) mRNA and protein expression in the macrophages, and these increases were suppressed by the ERK1/2 inhibitor PD98059 or ERK1/2 small interfering RNA (siRNA) treatment. OxLDL up-regulated the expression of peroxisome proliferator-activated receptor α (PPARα) at the mRNA and protein levels, which could be abolished by COX-2 siRNA or COX-2 inhibitor NS398 treatment in these macrophages. OxLDL dramatically elevated cellular cholesterol efflux, which was abrogated by inhibiting ERK1/2 and/or COX-2. In addition, oxLDL-induced NPC1 expression and cellular cholesterol efflux were reversed by PPARα siRNA or GW6471, an antagonist of PPARα. Taken together, these results provide the evidence that oxLDL can up-regulate the expression of the NPC1 through ERK1/2/COX-2/PPARα-signaling pathway in macrophages.
摘要：
Background Macrophage migration inhibitory factor (MIF) is an upstream regulator in immune and inflammatory responses. However, its role in viral myocarditis remains unknown. In this study, we investigated the role of the MIF in coxsackievirus B3 (CVB3)-induced myocarditis. Methods Mice were randomized into two groups receiving either Eagle’s minimal essential medium (EMEM, control group) or virus solution (infected group). Subsets of mice in the infected group were sacrificed on days 3, 7, 14 and 28 after inoculation. Expression of MIF was detected using an enzyme-linked immunosorbent assay (ELISA), reverse transcription polymerase chain reaction and immunohistochemistry. A neutralizing antibody (Ab) to MIF was injected intraperitoneally from day 0 to 7 after inoculation. Disease severity was estimated by histopathology of the heart and by the heart weight to body weight ratio, and the interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α) in the myocardium were measured by ELISA on day 14. Results The serum MIF concentration and expression levels of myocardial MIF mRNA and protein were significantly elevated in mice on days 7 and 14 post-infection. The survival rate was markedly higher and disease severity was obviously less in mice treated with anti-MIF Ab. Furthermore, MIF blockade significantly decreased the IL-1β and TNF-α in the myocarditic heart. Conclusion These results demonstrate that MIF is an important naturally occurring inflammatory cytokine in CVB3-induced myocarditis, and anti-MIF Ab may lessen the inflammatory response.
期刊：
JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH,2011年65(8):722-726 ISSN：0143-005X
通讯作者：
Wen, S. W.
作者机构：
[Wen, S. W.; Guo, Y.; Walker, M.; Xie, R-H] Univ Ottawa, OMNI Res Grp, Dept Obstet & Gynecol, Fac Med, Ottawa, ON K1H 8L6, Canada.;[Wen, S. W.; Guo, Y.; Walker, M.; Xie, R-H] Ottawa Hosp Res Inst, Clin Epidemiol Program, Ottawa, ON, Canada.;[Xie, R-H] Huaihua Med Coll, Dept Nursing, Huaihua, Peoples R China.;[Wen, S. W.; Liao, S.; Guo, Y.] Cent S Univ, Sch Publ Hlth, Changsha, Hunan, Peoples R China.;[Xie, H.] Univ S China, Sch Nursing, Hengyang, Hunan, Peoples R China.
通讯机构：
[Wen, S. W.] U;Univ Ottawa, OMNI Res Grp, Dept Obstet & Gynecol, Fac Med, 501 Smyth Rd,Box 241, Ottawa, ON K1H 8L6, Canada.
摘要：
Objectives To assess the impact of prenatal and postnatal family support on the association between infant sex and postpartum depression (PPD). Design Prospective cohort study. Setting Pregnant women seen at Hunan Maternal and Infant Hospital, the First Affiliated and the Third Affiliated Hospitals of the Central South University in Changsha, Hunan, People's Republic of China from February to September 2007. Participants 534 Pregnant women who were consecutively recruited from the participating hospital during their prenatal visits at 30-32 weeks of gestation and who completed the 2 weeks postpartum survey, with no recorded major psychiatric disorders and obstetric and/or pregnancy complications. Main outcome measure PPD, which was defined as a score of 13 or higher of the Edinburgh Postnatal Depression Scale. Results Postnatal family support scores were much lower in women who gave birth to a female infant, and the OR of PPD was 3.67 (95% CI 2.31 to 5.84) for them as compared to women who gave birth to a male infant. After adjusting by postnatal support from all family members, husband and parents, the ORs of PPD for women who gave birth to a female infant decreased to 2.06 (95% CI 1.20 to 3.53), 2.89 (95% CI 1.76 to 4.77) and 2.20 (95% CI 1.28 to 3.77), respectively. Discussion Increased risk of PPD in Chinese women who gave birth to a female infant can be explained to large extent by inadequate or poor postpartum support from family members, particularly husband and parents.
