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Enhancement of Antibody-Induced Arthritis via Toll-Like Receptor 2 Stimulation Is Regulated by Granulocyte Reactive Oxygen Species

Kelkka, Tiina; Hultqvist, Malin LU ; Kutty Selva, Nandakumar LU and Holmdahl, Rikard LU (2012) In American Journal of Pathology 181(1). p.141-150
Abstract
The suppressive role of phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX2) complex-derived reactive oxygen species (ROS) in adaptive immunity-driven arthritis models is well established. In this study, we aimed to investigate the role of NOX2 complex-derived ROS In a model of innate immunity-driven arthritis and to identify the ROS-regulated innate receptors that control arthritis. We used collagen antibody-induced arthritis (CAIA), which is a T and B lymphocyte-independent model of the effector phase of arthritis and is induced by well-defined monoclonal arthritogenic antibodies and enhanced by injection of lipopolysaccharide (LPS). CAIA was induced in both wild-type and Ncf1 mutant mice that lack phagocyte... (More)
The suppressive role of phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX2) complex-derived reactive oxygen species (ROS) in adaptive immunity-driven arthritis models is well established. In this study, we aimed to investigate the role of NOX2 complex-derived ROS In a model of innate immunity-driven arthritis and to identify the ROS-regulated innate receptors that control arthritis. We used collagen antibody-induced arthritis (CAIA), which is a T and B lymphocyte-independent model of the effector phase of arthritis and is induced by well-defined monoclonal arthritogenic antibodies and enhanced by injection of lipopolysaccharide (LPS). CAIA was induced in both wild-type and Ncf1 mutant mice that lack phagocyte oxidative burst, and stimulated with LPS and other agents to activate innate immune responses. We found that both LPS and lipomannan enhanced CAIA more potently in the presence of functional phagocyte ROS production than in its absence. The ROS-dependent enhancement of CAIA was regulated by TLR2, but not by TLR4 stimulation, and was driven by granulocytes, whereas macrophages did not contribute to the phenotype. In addition, we report that collagen-induced arthritis was not affected by the functionality of the TLR4. We report that TLR2 signaling as an important ROS-regulated proinflammatory pathway leads to severe neutrophil-dependent inflammation in murine CAIA and conclude that the TLR2 pathway is modulated by phagocyte ROS to stimulate the development of arthritis. (Am J Pathol 2012,181: 141-150; http://dx.doi.org/10.1016/j.ajpath.2012.03.031) (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
American Journal of Pathology
volume
181
issue
1
pages
141 - 150
publisher
American Society for Investigative Pathology
external identifiers
  • wos:000305851100015
  • scopus:84862668677
ISSN
1525-2191
DOI
10.1016/j.ajpath.2012.03.031
language
English
LU publication?
yes
id
ec8945c7-3997-4190-b11c-4594074ea9f4 (old id 3001406)
date added to LUP
2012-09-03 07:19:52
date last changed
2017-11-19 03:21:13
@article{ec8945c7-3997-4190-b11c-4594074ea9f4,
  abstract     = {The suppressive role of phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX2) complex-derived reactive oxygen species (ROS) in adaptive immunity-driven arthritis models is well established. In this study, we aimed to investigate the role of NOX2 complex-derived ROS In a model of innate immunity-driven arthritis and to identify the ROS-regulated innate receptors that control arthritis. We used collagen antibody-induced arthritis (CAIA), which is a T and B lymphocyte-independent model of the effector phase of arthritis and is induced by well-defined monoclonal arthritogenic antibodies and enhanced by injection of lipopolysaccharide (LPS). CAIA was induced in both wild-type and Ncf1 mutant mice that lack phagocyte oxidative burst, and stimulated with LPS and other agents to activate innate immune responses. We found that both LPS and lipomannan enhanced CAIA more potently in the presence of functional phagocyte ROS production than in its absence. The ROS-dependent enhancement of CAIA was regulated by TLR2, but not by TLR4 stimulation, and was driven by granulocytes, whereas macrophages did not contribute to the phenotype. In addition, we report that collagen-induced arthritis was not affected by the functionality of the TLR4. We report that TLR2 signaling as an important ROS-regulated proinflammatory pathway leads to severe neutrophil-dependent inflammation in murine CAIA and conclude that the TLR2 pathway is modulated by phagocyte ROS to stimulate the development of arthritis. (Am J Pathol 2012,181: 141-150; http://dx.doi.org/10.1016/j.ajpath.2012.03.031)},
  author       = {Kelkka, Tiina and Hultqvist, Malin and Kutty Selva, Nandakumar and Holmdahl, Rikard},
  issn         = {1525-2191},
  language     = {eng},
  number       = {1},
  pages        = {141--150},
  publisher    = {American Society for Investigative Pathology},
  series       = {American Journal of Pathology},
  title        = {Enhancement of Antibody-Induced Arthritis via Toll-Like Receptor 2 Stimulation Is Regulated by Granulocyte Reactive Oxygen Species},
  url          = {http://dx.doi.org/10.1016/j.ajpath.2012.03.031},
  volume       = {181},
  year         = {2012},
}