Reactive oxygen species-mediated killing of activated fibroblasts by arsenic trioxide ameliorates fibrosis in a murine model of systemic sclerosis

Arthritis and Rheumatism
Niloufar KavianFrédéric Batteux

Abstract

In patients with systemic sclerosis (SSc), activated fibroblasts produce reactive oxygen species (ROS) that stimulate their proliferation and collagen synthesis. By analogy with tumor cells that undergo apoptosis upon cytotoxic treatment that increases ROS levels beyond a lethal threshold, we tested whether activated fibroblasts could be selectively killed by the cytotoxic molecule arsenic trioxide (As(2) O(3) ) in a murine model of SSc. SSc was induced in BALB/c mice by daily intradermal injections of HOCl. Mice were simultaneously treated with daily intraperitoneal injections of As(2) O(3) . As(2) O(3) limited dermal thickness and inhibited collagen deposition, as assessed by histologic examination and measurement of mouse skin and lung collagen contents. As(2) O(3) abrogated vascular damage, as shown by serum vascular cell adhesion molecule 1 level, and inhibited the production of autoantibodies, interleukin-4 (IL-4), and IL-13 by activated T cells. These beneficial effects were mediated through ROS generation that selectively killed activated fibroblasts containing low levels of glutathione. Our findings indicate that treatment with As(2) O(3) dramatically improves skin and lung fibrosis in a mouse model of SSc, providing a...Continue Reading

References

Jan 1, 1993·Chemical Research in Toxicology·N ScottD E Carter
Jan 25, 2002·Blood·Martin S TallmanJacob M Rowe
May 16, 2002·Seminars in Hematology·Kelly DavisonWilson H Miller
Jan 15, 2004·The Journal of Clinical Investigation·Yoshihide AsanoKunihiko Tamaki
Apr 9, 2004·Proceedings of the National Academy of Sciences of the United States of America·Wen-Chien ChouChi V Dang
Jul 24, 2004·The Journal of Biological Chemistry·Masatoshi JinninKunihiko Tamaki
Jun 23, 2006·The New England Journal of Medicine·Silvia Svegliati BaroniArmando Gabrielli
May 3, 2008·The Journal of Pharmacology and Experimental Therapeutics·Wai-Pui TseZhi-Xiu Lin
Nov 6, 2008·Clinics in Liver Disease·R UrtasunN Nieto
Mar 10, 2009·Journal of Gastroenterology·Atsushi Masamune, Tooru Shimosegawa
Apr 22, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Amélie ServettazFrédéric Batteux

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Citations

Aug 21, 2013·PloS One·Pietro SantulliDidier Borderie
Sep 3, 2014·La Presse médicale·Nicolas DumoitierLuc Mouthon
Aug 16, 2014·Life Sciences·Shu-Yan GaoChang-Jun Lv
Nov 18, 2014·Current Pathobiology Reports·Anjali ShroffJared Jagdeo
Nov 30, 2013·Arthritis Research & Therapy·Wioleta MarutFrédéric Batteux
Sep 22, 2015·Expert Opinion on Therapeutic Targets·Pietro SantulliCharles Chapron
Nov 29, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Claus Jacob
Jul 5, 2015·Seminars in Immunopathology·Ellen De Langhe, Rik Lories
Mar 31, 2015·Pathologie-biologie·T Hua-Huy, A T Dinh-Xuan
May 22, 2016·Clinical Reviews in Allergy & Immunology·Alexandre T J MariaPhilippe Guilpain
Oct 16, 2019·Naunyn-Schmiedeberg's Archives of Pharmacology·Abdalkareem Omar MaghmomehNoha Abdel-Rahman
Feb 6, 2020·British Journal of Pharmacology·Yishan YeFlorent Malard
Oct 16, 2016·Oncotarget·Jessica E MillerChandrakant Tayade
Sep 11, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Florence MorinFrédéric Batteux
Dec 13, 2019·Nature Communications·Mohamed JeljeliFrédéric Batteux
May 10, 2017·Molecular Human Reproduction·Iñaki González-ForuriaFrédéric Batteux
Sep 21, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Niloufar KavianFrédéric Batteux
Jun 4, 2020·Clinical & Translational Immunology·Yishan YeFlorent Malard
Aug 7, 2021·Advanced Drug Delivery Reviews·Huan XuLeaf Huang

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