Faculty Opinions recommendation of Joint tissues amplify inflammation and alter their invasive behavior via leukotriene B4 in experimental inflammatory arthritis.

2010 ◽  
Author(s):  
Richard L Stevens
Keyword(s):  
Inflammatory Arthritis ◽  
Leukotriene B4 ◽  
Invasive Behavior

scholarly journals Novel protective role for MAP kinase phosphatase 2 in inflammatory arthritis

RMD Open ◽  
2019 ◽  
Vol 5 (1) ◽  
pp. e000711
Author(s):  
Juliane Schroeder ◽  
Kirsty Ross ◽  
Kathryn McIntosh ◽  
Shilan Jabber ◽  
Stuart Woods ◽  
...  
Keyword(s):  
Inflammatory Arthritis ◽  
Neutrophil Migration ◽  
Protective Role ◽  
Leukotriene B4 ◽  
Mitogen Activated Protein Kinase ◽  
Wild Type ◽  
Map Kinase Phosphatase ◽  
Tnf Α ◽  
The Impact

ObjectivesWe have previously shown mitogen-activated protein kinase phosphatase 2 (MKP-2) to be a key regulator of proinflammatory cytokines in macrophages. In the study presented here, we investigated the role of MKP-2 in inflammatory arthritis with a particular focus on neutrophils.MethodsTo achieve this, we subjected MKP-2 deficient and wild type mice to collagen antibody induced arthritis, an innate model of arthritis, and determined disease pathology. To further our investigation, we depleted neutrophils in a prophylactic and therapeutic fashion. Last, we used chemotaxis assays to analyse the impact of MKP-2 deletion on neutrophil migration.ResultsMKP-2-/- mice showed a significant increase in disease pathology linked to elevated levels of proarthritic cytokines and chemokines TNF-α, IL-6 and MCP-1 in comparison to wild type controls. This phenotype is prevented or abolished after administration of neutrophil depleting antibody prior or after onset of disease, respectively. While MCP-1 levels were not affected, neutrophil depletion diminished TNF-α and reduced IL-6, thus linking these cytokines to neutrophils. In vivo imaging showed that MKP-2-/- mice had an increased influx of neutrophils into affected joints, which was higher and potentially prolonged than in wild type animals. Furthermore, using chemotaxis assays we revealed that MKP-2 deficient neutrophils migrate faster towards a Leukotriene B4 gradient. This process correlated with a reduced phosphorylation of ERK in MKP-2-/- neutrophils.ConclusionsThis is the first study to show a protective role for MKP-2 in inflammatory arthritis.

scholarly journals Neutrophil-derived leukotriene B4 is required for inflammatory arthritis

2006 ◽  
Vol 203 (4) ◽  
pp. 837-842 ◽  
Author(s):  
Mei Chen ◽  
Bing K. Lam ◽  
Yoshihide Kanaoka ◽  
Peter A. Nigrovic ◽  
Laurent P. Audoly ◽  
...  
Keyword(s):  
Inflammatory Arthritis ◽  
Leukotriene B4 ◽  
Transfer Model ◽  
Effector Functions ◽  
Serum Transfer ◽  
Cellular Source ◽  
Disease Induction ◽  
Deficient Mice ◽  
Arthritis Susceptibility ◽  
Serum Transfer Model

Neutrophils serve as a vanguard of the acute innate immune response to invading pathogens. Neutrophils are also abundant at sites of autoimmune inflammation, such as the rheumatoid joint, although their pathophysiologic role is incompletely defined and relevant effector functions remain obscure. Using genetic and pharmacologic approaches in the K/BxN serum transfer model of arthritis, we find that autoantibody-driven erosive synovitis is critically reliant on the generation of leukotrienes, and more specifically on leukotriene B4 (LTB4), for disease induction as well as perpetuation. Pursuing the cellular source for this mediator, we find via reconstitution experiments that mast cells are a dispensable source of leukotrienes, whereas arthritis susceptibility can be restored to leukotriene-deficient mice by intravenous administration of wild-type neutrophils. These experiments demonstrate a nonredundant role for LTB4 in inflammatory arthritis and define a neutrophil mediator involved in orchestrating the synovial eruption.

scholarly journals Joint Tissues Amplify Inflammation and Alter Their Invasive Behavior via Leukotriene B4in Experimental Inflammatory Arthritis

2010 ◽  
Vol 185 (9) ◽  
pp. 5503-5511 ◽  
Author(s):  
Mei Chen ◽  
Bing K. Lam ◽  
Andrew D. Luster ◽  
Simona Zarini ◽  
Robert C. Murphy ◽  
...  
Keyword(s):  
Inflammatory Arthritis ◽  
Invasive Behavior

scholarly journals Nonredundant Roles for Leukotriene B4 Receptors BLT1 and BLT2 in Inflammatory Arthritis

2010 ◽  
Vol 185 (5) ◽  
pp. 3049-3056 ◽  
Author(s):  
Steven P. Mathis ◽  
Venkatakrishna R. Jala ◽  
David M. Lee ◽  
Bodduluri Haribabu
Keyword(s):  
Inflammatory Arthritis ◽  
Leukotriene B4

scholarly journals A unique requirement for the leukotriene B4 receptor BLT1 for neutrophil recruitment in inflammatory arthritis

2006 ◽  
Vol 203 (4) ◽  
pp. 829-835 ◽  
Author(s):  
Nancy D. Kim ◽  
Richard C. Chou ◽  
Edward Seung ◽  
Andrew M. Tager ◽  
Andrew D. Luster
Keyword(s):  
Inflammatory Arthritis ◽  
Biological Response ◽  
Joint Inflammation ◽  
Leukotriene B4 ◽  
Neutrophil Recruitment ◽  
Chemokine Production ◽  
Activated Neutrophils ◽  
Established Disease ◽  
Leukotriene B4 Receptor ◽  
Redundant Role

Neutrophil recruitment into tissue plays an important role in host defense and disease pathogenesis, including the inflammatory arthritides. A multitude of diverse chemoattractants have been implicated in neutrophil recruitment, suggesting that they have overlapping functions in mediating this critical biological response. However, here we demonstrate a unique, non-redundant role for the leukotriene B4 receptor BLT1 in mediating neutrophil recruitment into the joint in the K/BxN mouse model of inflammatory arthritis. We demonstrate that neutrophil expression of BLT1 was absolutely required for arthritis generation and chemokine production in this model, and that specific BLT1 inhibition reversed established disease. Adoptive transfer of wild-type (WT) neutrophils restored arthritis and chemokine production in BLT1−/− mice. Surprisingly, the primary effect of the transferred WT neutrophils into BLT1−/− mice was to promote the entry of endogenous BLT1−/− neutrophils into the joints of these mice. However, continued joint inflammation was dependent on the presence of WT neutrophils, indicating an ongoing specific requirement for BLT1-activated neutrophils in mediating BLT1−/− neutrophil recruitment by other chemoattractants. These experiments demonstrate that neutrophil BLT1 functions in a novel and essential non–cell-autonomous manner to enable the recruitment of additional neutrophils not expressing this receptor, thereby amplifying the inflammatory response in autoantibody-induced arthritis.

Sign in / Sign up

Export Citation Format

Share Document