Back to Search
Start Over
Myeloid related protein induces muscle derived inflammatory mediators in juvenile dermatomyositis
- Source :
- Arthritis Research and Therapy, Arthritis Research and Therapy, BioMed Central, 2013, 15 (5), pp.R131. ⟨10.1186/ar4311⟩, Arthritis Research and Therapy, 2013, 15 (5), pp.R131, Arthritis Research and Therapy, BioMed Central, 2013, 15 (5), pp.R131, Arthritis Research and Therapy, 2013, 15 (5), pp.R131. ⟨10.1186/ar4311⟩, Arthritis Research & Therapy
- Publication Year :
- 2013
- Publisher :
- HAL CCSD, 2013.
-
Abstract
- International audience; IntroductionThe aetiopathogenesis of juvenile dermatomyositis (JDM) remains poorly understood. In particular the contribution of monocytes or macrophages, which are frequently observed to be an infiltrate within muscle tissue very early in the disease process, is unknown. We hypothesised that these cells secrete the pro-inflammatory myeloid related protein (MRP) 8/14 which may then contribute to muscle pathology in JDM.MethodsIn this study of 56 JDM patients, serum MRP8/14 levels were compared with clinical measures of disease activity. Muscle biopsies taken early in disease were assessed by immunohistochemistry to determine the frequency and identity of MRP-expressing cells. The effects of MRP stimulation and endoplasmic reticulum (ER) stress on muscle were tested in vitro. Serum or supernatant levels of cytokines were analyzed by multiplex immunoassay.ResultsSerum MRP8/14 correlated with physician's global assessment of disease activity in JDM (R = 0.65, p = 0.0003) and muscle strength/endurance, childhood myositis assessment score (CMAS, R = −0.55, p = 0.004). MRP8/14 was widely expressed by CD68+ macrophages in JDM muscle tissue. When cultured with human myoblasts, MRP8 led to the secretion of MCP-1 and IL-6, which was enhanced by ER stress. Both inflammatory mediators were detected in significantly higher levels in the serum of JDM patients compared to healthy controls.ConclusionsThis study is the first to identify serum MRP8/14 as a potential biomarker for disease activity in JDM. We propose that tissue infiltrating macrophages secreting MRP8/14 may contribute to myositis, by driving the local production of cytokines directly from muscle.
- Subjects :
- Male
Myeloid
Biopsy
Gene Expression
0302 clinical medicine
Interferon
Immunology and Allergy
Myocyte
Child
Chemokine CCL2
Juvenile dermatomyositis
0303 health sciences
[SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system
biology
Reverse Transcriptase Polymerase Chain Reaction
Muscles
Endoplasmic Reticulum Stress
Immunohistochemistry
3. Good health
medicine.anatomical_structure
[SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system
Child, Preschool
Cytokines
Female
Inflammation Mediators
Research Article
medicine.drug
Muscle tissue
Adolescent
Myoblasts, Skeletal
Immunology
Antigens, Differentiation, Myelomonocytic
Dermatomyositis
Cell Line
03 medical and health sciences
[SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics
Rheumatology
Downregulation and upregulation
Antigens, CD
medicine
Calgranulin B
Humans
Calgranulin A
Muscle Strength
Interleukin 6
030304 developmental biology
030203 arthritis & rheumatology
[SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics
Interleukin-6
business.industry
Macrophages
medicine.disease
Microscopy, Fluorescence
biology.protein
business
Subjects
Details
- Language :
- English
- ISSN :
- 14786354
- Database :
- OpenAIRE
- Journal :
- Arthritis Research and Therapy, Arthritis Research and Therapy, BioMed Central, 2013, 15 (5), pp.R131. ⟨10.1186/ar4311⟩, Arthritis Research and Therapy, 2013, 15 (5), pp.R131, Arthritis Research and Therapy, BioMed Central, 2013, 15 (5), pp.R131, Arthritis Research and Therapy, 2013, 15 (5), pp.R131. ⟨10.1186/ar4311⟩, Arthritis Research & Therapy
- Accession number :
- edsair.doi.dedup.....9c288bc65255c9eb1c4bccb0154ad1d4