Interleukin Expression after Injury and the Effects of Interleukin-1 Receptor Antagonist

Autor: Stacey Brickson, Ray Vanderby, Connie S. Chamberlain, Ellen M. Leiferman, William L. Murphy, Kayt E. Frisch, Geoffrey S. Baer
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Male
Pathology
Anatomy and Physiology
Angiogenesis
Microarrays
medicine.medical_treatment
lcsh:Medicine
Veterinary Anatomy and Physiology
Monocytes
0302 clinical medicine
Engineering
Animal Musculoskeletal Anatomy
Fibrosis
Molecular Cell Biology
lcsh:Science
Musculoskeletal System
Oligonucleotide Array Sequence Analysis
0303 health sciences
Multidisciplinary
Chemistry
Interleukin
Granulation tissue
Genomics
Animal Models
Collateral Ligaments
Biomechanical Phenomena
Veterinary Surgery
medicine.anatomical_structure
Cytokine
Cytokines
Collagen
medicine.symptom
Research Article
Veterinary Medicine
medicine.medical_specialty
Histology
Immune Cells
Immunology
Biomedical Engineering
Inflammation
Bioengineering
Cell Growth
03 medical and health sciences
Cicatrix
Model Organisms
medicine
Animals
Rats
Wistar
Biology
030304 developmental biology
Interleukins
Macrophages
lcsh:R
Immunity
Computational Biology
Receptors
Interleukin-1
medicine.disease
Rats
Interleukin 1 receptor antagonist
Gene Expression Regulation
Immune System
Cancer research
Rat
lcsh:Q
Veterinary Science
Wound healing
Genome Expression Analysis
030217 neurology & neurosurgery
Zdroj: PLoS ONE
PLoS ONE, Vol 8, Iss 8, p e71631 (2013)
ISSN: 1932-6203
Popis: Ligament healing follows a series of complex coordinated events involving various cell types, cytokines, as well as other factors, producing a mechanically inferior tissue more scar-like than native tissue. Macrophages provide an ongoing source of cytokines to modulate inflammatory cell adhesion and migration as well as fibroblast proliferation. Studying interleukins inherent to ligament healing during peak macrophage activation and angiogenesis may elucidate inflammatory mediators involved in subsequent scar formation. Herein, we used a rat healing model assayed after surgical transection of their medial collateral ligaments (MCLs). On days 3 and 7 post-injury, ligaments were collected and used for microarray analysis. Of the 12 significantly modified interleukins, components of the interleukin-1 family were significantly up-regulated. We therefore examined the influence of interleukin-1 receptor antagonist (IL-1Ra) on MCL healing. Transected rat MCLs received PBS or IL-1Ra at the time of surgery. Inhibition of IL-1 activation decreased pro-inflammatory cytokines (IL-1α, IL-1β, IL-12, IL-2, and IFN-γ), myofibroblasts, and proliferating cells, as well as increased anti-inflammatory cytokines (IL-10), endothelial cells/blood vessel lumen, M2 macrophages, and granulation tissue size without compromising the mechanical properties. These results support the concept that IL-1Ra modulates MCL-localized granulation tissue components and cytokine production to create a transient environment that is less inflammatory. Overall, IL-1Ra may have therapeutic potential early in the healing cascade by stimulating the M2 macrophages and altering the granulation tissue components. However, the single dose of IL-1Ra used in this study was insufficient to maintain the more regenerative early response. Due to the transient influence on most of the healing components tested, IL-1Ra may have greater therapeutic potential with sustained delivery.
Databáze: OpenAIRE
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