D provided evidence that this effect may be mediated through a

D provided evidence that this effect may be mediated through a cytotoxic activity against intimal smooth muscle cells [14]. In the present study we analyzed the role of CD8+ T cells in neointima formation in Tap10 mice that have severely reduced MHC class I expression and number of CD8+ T cells. However, in contrast to the studies by Dimayuga and coworkers we did not observe any effect on neointima formation. The reasons for the different outcomes remain to be clarified but may involve differences in the models used. UKI-1 web Rag-12/2 mice are completely devoid of functional T and B cells, whereas Tap10 mice have both functional CD4+ T cells and B cells. Since B cells previously has been shown to reduce neointima formationin Rag-12/2 mice [12] it is possible that the B cells present in Tap10 mice are sufficient to suppress any enhanced neointima formation due to lack of CD8+ T cells in these mice. It should also be kept in mind that although the CD8+ T cells constitute less than 1 of the total KDM5A-IN-1 site lymphocyte population in Tap10 mice [20], these mice still have the ability to generate a small population of functionally intact CD8+ T cells [21] that may have affected neointima formation in our studies. In conclusion, the present observations demonstrate that carotid injury is associated with pro-inflammatory responses, such as activation of CD4+IFNc+ Th1 cells and IL-1b release, but also mobilization of potentially anti-inflammatory CD4+CD25+FoxP3+ Tregs. Depletion of Tregs did not, however, influence the subsequent repair processes leading to the formation of a neointima. They also demonstrate that lack of CD8+ T cells does not influence neointima formation in the presence of functional CD4+ T cells and B cells.Author ContributionsConceived and designed the experiments: JN. Performed the experiments: ??AS HB AS KEB MFG GNF AHN. Analyzed the data: AS HB AS SR KEB MFG GNF AHN. Wrote the 1531364 paper: JN. Critical revision of the ?manuscript: AS HB AS SR KEB MFG GNF AHN.
Ovarian cancer has the highest fatality rate of all female reproductive system malignancies, and in 2008 there were an estimated 225,500 new cases and 140,200 deaths worldwide [1]. As is the case for many malignancies, ovarian cancer is a multifactorial disease, and hormonal factors, wound healing and inflammation may all play a role in its development. Interactions between the environment and genetic factors also play significant roles [2]. Many studies have investigated the genetic basis of ovarian cancer susceptibility. For example, BRCA1, BRCA2, MLH1, MSH2, RAD51C, RAD51D, RB1, SMAD6, CASP8, and LIN28B have all been implicated in ovarian cancer [3,4,5,6,7,8,9,10]. Recently, genome-wide association studies (GWAS) have found strong associations between ovarian cancer and several common susceptibility alleles in four loci [11,12,13]. Braem et al. reviewed 147 candidate genes, and the 3 GWAS studies published from 1990 to October 2010 identified approximately 1100 genetic variants in more than 200 candidate genes and 20 intergenic regions [8]. However, the relationships between known genetic variants and ovarian cancer are limited, and more studies need be performed to elucidate causal genetic variants and facilitate the identification of high risk subgroups within the general population [5]. MTDH, also known as astrocyte elevated gene-1 (AEG-1) and Lyric, was originally identified as an HIV-inducible gene in primary human fetal astrocytes [14]. MTDH is located at 8q22,consists of 12 exons and.D provided evidence that this effect may be mediated through a cytotoxic activity against intimal smooth muscle cells [14]. In the present study we analyzed the role of CD8+ T cells in neointima formation in Tap10 mice that have severely reduced MHC class I expression and number of CD8+ T cells. However, in contrast to the studies by Dimayuga and coworkers we did not observe any effect on neointima formation. The reasons for the different outcomes remain to be clarified but may involve differences in the models used. Rag-12/2 mice are completely devoid of functional T and B cells, whereas Tap10 mice have both functional CD4+ T cells and B cells. Since B cells previously has been shown to reduce neointima formationin Rag-12/2 mice [12] it is possible that the B cells present in Tap10 mice are sufficient to suppress any enhanced neointima formation due to lack of CD8+ T cells in these mice. It should also be kept in mind that although the CD8+ T cells constitute less than 1 of the total lymphocyte population in Tap10 mice [20], these mice still have the ability to generate a small population of functionally intact CD8+ T cells [21] that may have affected neointima formation in our studies. In conclusion, the present observations demonstrate that carotid injury is associated with pro-inflammatory responses, such as activation of CD4+IFNc+ Th1 cells and IL-1b release, but also mobilization of potentially anti-inflammatory CD4+CD25+FoxP3+ Tregs. Depletion of Tregs did not, however, influence the subsequent repair processes leading to the formation of a neointima. They also demonstrate that lack of CD8+ T cells does not influence neointima formation in the presence of functional CD4+ T cells and B cells.Author ContributionsConceived and designed the experiments: JN. Performed the experiments: ??AS HB AS KEB MFG GNF AHN. Analyzed the data: AS HB AS SR KEB MFG GNF AHN. Wrote the 1531364 paper: JN. Critical revision of the ?manuscript: AS HB AS SR KEB MFG GNF AHN.
Ovarian cancer has the highest fatality rate of all female reproductive system malignancies, and in 2008 there were an estimated 225,500 new cases and 140,200 deaths worldwide [1]. As is the case for many malignancies, ovarian cancer is a multifactorial disease, and hormonal factors, wound healing and inflammation may all play a role in its development. Interactions between the environment and genetic factors also play significant roles [2]. Many studies have investigated the genetic basis of ovarian cancer susceptibility. For example, BRCA1, BRCA2, MLH1, MSH2, RAD51C, RAD51D, RB1, SMAD6, CASP8, and LIN28B have all been implicated in ovarian cancer [3,4,5,6,7,8,9,10]. Recently, genome-wide association studies (GWAS) have found strong associations between ovarian cancer and several common susceptibility alleles in four loci [11,12,13]. Braem et al. reviewed 147 candidate genes, and the 3 GWAS studies published from 1990 to October 2010 identified approximately 1100 genetic variants in more than 200 candidate genes and 20 intergenic regions [8]. However, the relationships between known genetic variants and ovarian cancer are limited, and more studies need be performed to elucidate causal genetic variants and facilitate the identification of high risk subgroups within the general population [5]. MTDH, also known as astrocyte elevated gene-1 (AEG-1) and Lyric, was originally identified as an HIV-inducible gene in primary human fetal astrocytes [14]. MTDH is located at 8q22,consists of 12 exons and.