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Dynamics of local gene regulations in synovial fluid leukocytes from horses with lipopolysaccharide-induced arthritis

Walters, Marie and Skovgaard, Kerstin and Andersen, Pia Haubro and Heegaard, Peter M. H. and Jacobsen, Stine (2021). Dynamics of local gene regulations in synovial fluid leukocytes from horses with lipopolysaccharide-induced arthritis. Veterinary Immunology and Immunopathology. 241 , 110325
[Research article]

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Abstract

The role of resident cells such a synoviocytes and chondrocytes in intra-articular inflammation is wellcharacterized, however the in vivo gene expression patterns of cells (predominantly leukocytes) in the synovial fluid (SF) of an inflamed joint have never previously been investigated. The aim of this study was to investigate gene expression in SF leukocytes from the inflamed joint cavity after intra-articular lipopolysaccharide (LPS) injection in horses to improve our understanding of the temporal regulation of the intra-articular inflammatory response. Gene expression was investigated in SF samples available from six horses 2, 4, 8 16 and 24 h after experimental induction of inflammation in the radiocarpal joint by lipopolysaccharide (LPS) injection. Leukocytic expression of 43 inflammation-related genes was studied using microfluidic high throughput qPCR (Fluidigm (R)). Expression of 26 genes changed significantly over the 24 h study period, including pro- and antiinflammatory genes such as interleukin (IL)1, IL6, tumor necrosis factor (TNF), cyclooxygenase 2 (COX2), IL1 receptor antagonist (IL1RN), IL10, and superoxide dismutase 2 (SOD2), chemokine genes, apoptosis-related genes, and genes related to cartilage turnover (matrix metalloproteinase 8 and tissue inhibitor of metalloproteinase 1). The inflammatory responses appeared to be regulated, as an early increase (at 2 h) in expression of the pro-inflammatory genes IL1, IL6, TNF and COX2 was rapidly followed by increased expression (at 4 h) of several anti-inflammatory genes (IL10, IL1RN and SOD2). Similarly, both pro- and anti-apoptotic gene expression as well as expression of chondrodegenerative and chondroprotective genes were activated in SF leukocytes. Thus, the inflammatory response in leukocytes infiltrating the joint in the acute stage of arthritis was well orchestrated in this single-hit LPS-induced arthritis model. This study is the first to describe gene expression patterns in SFderived leukocytes in vivo during severe joint inflammation, and the results thus expand our knowledge of basic inflammatory mechanisms in the early local response in an inflamed joint.

Authors/Creators:Walters, Marie and Skovgaard, Kerstin and Andersen, Pia Haubro and Heegaard, Peter M. H. and Jacobsen, Stine
Title:Dynamics of local gene regulations in synovial fluid leukocytes from horses with lipopolysaccharide-induced arthritis
Series Name/Journal:Veterinary Immunology and Immunopathology
Year of publishing :2021
Volume:241
Article number:110325
Number of Pages:9
Publisher:ELSEVIER
ISSN:0165-2427
Language:English
Publication Type:Research article
Article category:Scientific peer reviewed
Version:Published version
Copyright:Creative Commons: Attribution 4.0
Full Text Status:Public
Subjects:(A) Swedish standard research categories 2011 > 4 Agricultural Sciences > 403 Veterinary Science > Clinical Science
Keywords:Leukocytes, Gene expression, Joint, Inflammation, Arthritis, Horses
URN:NBN:urn:nbn:se:slu:epsilon-p-114048
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-p-114048
Additional ID:
Type of IDID
DOI10.1016/j.vetimm.2021.110325
Web of Science (WoS)000704337900001
ID Code:25895
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
Department:(VH) > Dept. of Clinical Sciences
Deposited By: SLUpub Connector
Deposited On:21 Oct 2021 12:25
Metadata Last Modified:21 Oct 2021 12:31

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