title: HIV Exposure to the Epithelia in Ectocervical and Colon Tissues Induces Inflammatory Cytokines Without Tight Junction Disruption.
abstract: Epithelial cells in human cervical and colonic mucosa do not express HIV receptor. However, HIV transmission occurs across the unbreached epithelia by an unknown mechanism. In this study, the effect of HIV exposure on tight junction (TJ) and cytokine production in ectocervical and colon mucosal epithelia in tissue biopsies was investigated in an organ culture model. After HIV exposure, the distribution patterns and quantities of epithelial TJ and adherens proteins were evaluated by immunofluorescence staining followed by confocal microscopy. Cytokine mRNA in the mucosal epithelia was also evaluated by real-time reverse transcription-polymerase chain reaction (RT-PCR). HIV transmission was evaluated by measuring p24 production in culture supernatant. Our results showed there were no significant changes in the distribution and quantities of epithelial TJ/adherens junction (AJ) proteins after exposure to HIV. However, higher levels of CXCL10 and CXCL11 mRNA expression were detected in HIV-exposed ectocervical epithelia. In case of colon mucosa, higher levels of CXCL10 and IL-6 mRNA expression were detected in HIV-exposed colon mucosa. Our study suggests that HIV induces cytokine production in epithelial cells, which may facilitate HIV transmission by recruiting HIV target cells in the submucosal region. Furthermore, HIV transmission may not occur through epithelial TJ/AJ disruption.
authors.affiliation: 1 Department of Infectious Diseases and Microbiology, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Soni
authors.initials: S
authors.lastname: Sankapal
authors.affiliation: 1 Department of Infectious Diseases and Microbiology, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Phalguni
authors.initials: P
authors.lastname: Gupta
authors.affiliation: 1 Department of Infectious Diseases and Microbiology, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Deena
authors.initials: D
authors.lastname: Ratner
authors.affiliation: 1 Department of Infectious Diseases and Microbiology, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Ming
authors.initials: M
authors.lastname: Ding
authors.affiliation: 1 Department of Infectious Diseases and Microbiology, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Chengli
authors.initials: C
authors.lastname: Shen
authors.affiliation: 1 Department of Infectious Diseases and Microbiology, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Anwesha
authors.initials: A
authors.lastname: Sanyal
authors.affiliation: 2 Department of Cell Biology and Physiology, School of Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Donna
authors.initials: D
authors.lastname: Stolz
authors.affiliation: 3 Division of Infectious Diseases, Department of Medicine, Miriam Hospital/Alpert Medical School, Brown University , Providence, Rhode Island.|4 Division of Infectious Diseases, Department of Obstetrics and Gynecology, Miriam Hospital/Alpert Medical School, Brown University , Providence, Rhode Island.
authors.forename: Susan
authors.initials: S
authors.lastname: Cu-Uvin
authors.affiliation: 3 Division of Infectious Diseases, Department of Medicine, Miriam Hospital/Alpert Medical School, Brown University , Providence, Rhode Island.|4 Division of Infectious Diseases, Department of Obstetrics and Gynecology, Miriam Hospital/Alpert Medical School, Brown University , Providence, Rhode Island.
authors.forename: Bharat
authors.initials: B
authors.lastname: Ramratnam
authors.affiliation: 1 Department of Infectious Diseases and Microbiology, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
mesh_terms: D002478:Cells, Cultured; D002584:Cervix Uteri / Q000276:immunology / Q000821:virology*; D003106:Colon / Q000276:immunology / Q000821:virology*; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D004848:Epithelium / Q000276:immunology / Q000821:virology*; D005260:Female; D020869:Gene Expression Profiling; D016655:HIV Core Protein p24 / Q000032:analysis; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013194:Staining and Labeling; D062725:Tight Junction Proteins / Q000032:analysis; D019108:Tight Junctions / Q000502:physiology*
chemical_list: D016207:Cytokines; D016655:HIV Core Protein p24; D062725:Tight Junction Proteins
keywords: HIV transmission; inflammatory cytokines; mucosal epithelia; tight junctions