Polyanionic microbicides modify Toll-like receptor-mediated cervicovaginal immune responses.

Antimicrobial Agents and Chemotherapy
R T TrifonovaR N Fichorova

Abstract

Topical microbicides are being developed as a preventative approach to reduce the sexual transmission of human immunodeficiency virus type 1 (HIV-1) and other infections. For them to be efficacious, it is believed that they should avoid inducing inflammation while allowing the vaginal epithelium to initiate protective Toll-like receptor (TLR)-mediated innate responses against pathogens. In this study, human cervical and vaginal epithelial cells were exposed to polyanionic HIV entry inhibitors and the following synthetic TLR ligands: (i) the bacterial lipoprotein Pam(3)CSK(4), binding cell surface TLR1/TLR2; (ii) macrophage activating lipopeptide 2 (MALP-2), binding cell surface TLR2/TLR6; and (iii) the viral double-stranded RNA analog poly(I:C), recognized by intracellular TLR3. Cell activation was assessed by nuclear factor kappaB (NF-kappaB) reporter gene transactivation and cytokine production. In spite of enhancing TLR-triggered NF-kappaB activation, the polyanionic microbicide compounds dextran sulfate and polystyrene sulfonate significantly inhibited TLR-mediated cytokine production. They decreased cytokine mRNA and protein levels of proinflammatory (interleukin-8 [IL-8] and IL-1beta) and antiviral (beta interferon) cytok...Continue Reading

References

Jul 1, 1995·Trends in Microbiology·S R HedgesC Svanborg
Nov 1, 1994·Journal of Leukocyte Biology·A HaradaK Matsushima
Oct 25, 1996·Annals of the New York Academy of Sciences·R S SelvanJ L Platt
Nov 30, 2000·Proceedings of the National Academy of Sciences of the United States of America·A OzinskyA Aderem
Jun 30, 2001·International Immunology·O TakeuchiS Akira
Jul 27, 2001·Proceedings of the National Academy of Sciences of the United States of America·S BauerG B Lipford
Sep 8, 2001·Nature Immunology·M SchnareR Medzhitov
Jan 25, 2002·Nature·Michael Zasloff
Feb 23, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Raina N FichorovaRobin R Ingalls
Mar 22, 2002·Nature Reviews. Immunology·R Medzhitov
Sep 11, 2002·Cytokine & Growth Factor Reviews·William P Arend
Nov 26, 2002·BMC Infectious Diseases·A Robert NeurathYun-Yao Li
Jan 14, 2003·Annual Review of Immunology·Kiyoshi TakedaShizuo Akira
Jul 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·André BáficaAlan Sher
Jan 31, 2004·Seminars in Immunology·Kiyoshi Takeda, Shizuo Akira
Mar 3, 2004·Biological & Pharmaceutical Bulletin·Masaru NakamuraYoshihiko Watanabe
Apr 20, 2004·Assay and Drug Development Technologies·Ralph R MartelBruce E Seligmann
May 14, 2004·Nucleic Acids Research·Bradley J TillSteven Henikoff
Oct 19, 2004·Molecular Immunology·Massimo Alfano, Guido Poli
Dec 9, 2004·International Immunology·Kiyoshi Takeda, Shizuo Akira
Apr 27, 2005·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Sharon L HillierFulvia Veronese
Aug 11, 2005·Current HIV/AIDS Reports·Gustavo Doncel, Christine Mauck
Sep 2, 2005·American Journal of Reproductive Immunology : AJRI·Todd M SchaeferCharles R Wira

❮ Previous
Next ❯

Citations

Jun 17, 2009·Antimicrobial Agents and Chemotherapy·Secondo SonzaGilda Tachedjian
Dec 20, 2012·MBio·Jacques RavelSteven L Zeichner
Aug 2, 2013·Sexually Transmitted Infections·Raina N FichorovaAndrew B Onderdonk
Jan 10, 2013·BMC Microbiology·Hidemi S YamamotoRaina N Fichorova
Jan 11, 2013·Clinical & Developmental Immunology·Johanne PoudrierMichel Roger
Apr 17, 2010·Mediators of Inflammation·Kaei Nasu, Hisashi Narahara
Mar 24, 2010·Antiviral Research·Joanna SaidTomas Bergström
Mar 13, 2016·Annals of Clinical Microbiology and Antimicrobials·Zenda Woodman
Jan 13, 2011·American Journal of Reproductive Immunology : AJRI·Charu Kaushic
Apr 11, 2015·Advanced Drug Delivery Reviews·Sophia G Antimisiaris, Spyridon Mourtas
Aug 1, 2012·Molecular Biology International·Karen W Buckheit, Robert W Buckheit
Dec 9, 2010·Antiviral Research·Florian Hladik, Gustavo F Doncel
Jul 28, 2013·AIDS Research and Human Retroviruses·Christine K MauckGustavo F Doncel
Jul 8, 2011·Current Opinion in HIV and AIDS·Rada EllegårdMarie Larsson
Apr 13, 2012·The Annals of Pharmacotherapy·Kristina E E RokasSharon B Weissman
Nov 22, 2015·The Journal of Biological Chemistry·Raina N FichorovaBibhuti N Singh
Dec 17, 2009·Biology of Reproduction·Brooke E HjelmMelissa M Herbst-Kralovetz
May 6, 2021·Aging Cell·Marta Rodriguez-GarciaCharles R Wira
Aug 24, 2021·Frontiers in Cellular and Infection Microbiology·Raina N FichorovaKenneth H Mayer

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

CRISPR Screens in Drug Resistance

CRISPR-Cas system enables the editing of genes to create or correct mutations. This feed focuses on the application of CRISPR-Cas system in high-throughput genome-wide screens to identify genes that may confer drug resistance.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

ApoE, Lipids & Cholesterol

Serum cholesterol, triglycerides, apolipoprotein B (APOB)-containing lipoproteins (very low-density lipoprotein (VLDL), immediate-density lipoprotein (IDL), and low-density lipoprotein (LDL), lipoprotein A (LPA)) and the total cholesterol/high-density lipoprotein (HDL) cholesterol ratio are all connected in diseases. Here is the latest research.