Herpes simplex virus type 2 infection of human epithelial cells induces CXCL9 expression and CD4+ T cell migration via activation of p38-CCAAT/enhancer-binding protein-β pathway.

نویسندگان

  • Wenjie Huang
  • Kai Hu
  • Sukun Luo
  • Mudan Zhang
  • Chang Li
  • Wei Jin
  • Yalan Liu
  • George E Griffin
  • Robin J Shattock
  • Qinxue Hu
چکیده

Recruitment of CD4(+) T cells to infection areas after HSV-2 infection may be one of the mechanisms that account for increased HIV-1 sexual transmission. Lymphocytes recruited by chemokine CXCL9 are known to be important in control of HSV-2 infection in mice, although the underlying mechanism remains to be addressed. Based on our observation that CXCL9 expression is augmented in the cervical mucus of HSV-2-positive women, in this study we demonstrate that HSV-2 infection directly induces CXCL9 expression in primary cervical epithelial cells and cell lines, the principal targets of HSV-2, at both mRNA and protein levels. Further studies reveal that the induction of CXCL9 expression by HSV-2 is dependent upon a binding site for C/EBP-β within CXCL9 promoter sequence. Furthermore, CXCL9 expression is promoted at the transcriptional level through phosphorylating C/EBP-β via p38 MAPK pathway, leading to binding of C/EBP-β to the CXCL9 promoter. Chemotaxis assays indicate that upregulation of CXCL9 expression at the protein level by HSV-2 infection enhances the migration of PBLs and CD4(+) T cells, whereas neutralization of CXCL9 or inhibition of p38-C/EBP-β pathway can significantly decrease the migration. Our data together demonstrate that HSV-2 induces CXCL9 expression in human cervical epithelial cells by activation of p38-C/EBP-β pathway through promoting the binding of C/EBP-β to CXCL9 promoter, which may recruit activated CD4(+) T cells to mucosal HSV-2 infection sites and potentially increase the risk of HIV-1 sexual transmission.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Up-Regulation of Integrinsn α2β1 and α3β1 Expression in Human Foreskin Fibroblast Cells after In-Vitro Infection with Herpes Simplex Virus Type 1

The interaction of Herpes Simplex Virus type 1 (HSV-1) with human fetal foreskin fibroblast (HFFF) cell was studied using a recent isolate of HSV-1 which was propagated in Hep-2 cells. HFFF cells were challenged with HSV-1 with a multiplicity of infection (MOI) of 1 virus/cell for 24 hours. Flow cytometric analysis demonstrated that HSV-1 challenged HFFF cells expressed increased levels of α2β1...

متن کامل

Genistein Induces Apoptosis and Inhibits Proliferation of HT29 Colon Cancer Cells

Soybean isoflavone genistein has multiple anticancer properties and its pro-apoptotic and anti-proliferative effects have been studied in different cancer cells. However, the mechanisms of action of genistein and its molecular targets on human colon cells have not been fully elucidated. Therefore, caspase-3 and p38 mitogen-activated protein kinase (p38 MAPK) as the main therapeutic targets...

متن کامل

Herpes Simplex Virus Type 1 Latency-Associated Transcript Reduces Human Neuroblastoma Cell Proliferation

Background and Aims: The latency-associated transcript (LAT) transcribed by latent Herpes Simplex Virus type-1 in neuron cells are able to influence their host cell pathways. While the most of previous studies were focused on anti-apoptotic effects of LAT, our investigation is making an effort to explore LAT potency on cell cycle pathway in neuroblastoma cell lines. Methods: The evaluation of L...

متن کامل

The Effect of Herpes Simplex Virus Virion Host Shutoff Gene- a New Suicide Gene- on Tumor Cells

Background: The herpes simplex virus (HSV) UL41 gene product, virion host shutoff (Vhs) protein, mediates the rapid degradation of both viral and cellular mRNA. This ability suggests that Vhs protein can be used as a suicide gene in cancer gene therapy applications. The recent reports have shown that the degradation of cellular mRNA during herpes simplex infection is selective. RNA containing A...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Journal of immunology

دوره 188 12  شماره 

صفحات  -

تاریخ انتشار 2012