Sex-Based Differences in Monocytic Lineage Cells Contribute to More Severe Collagen-Induced Arthritis in Female Rats Compared with Male Rats
Autor: | Ljubica Simić, Gordana Leposavić, Jelena Sopta, Biljana Bufan, Mirjana Nacka-Aleksić, Mirjana Dimitrijević, Jelena Kotur-Stevuljevic, Nevena Arsenović-Ranin, Ivan Pilipović, Duško Kosec |
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Rok vydání: | 2020 |
Předmět: |
Male
0301 basic medicine Cellular differentiation Osteoclasts Arthritis Antioxidants Monocytes CX3CR1 0302 clinical medicine Immunology and Allergy CD68 Cell Differentiation Oxidants Monocytes’ plasticity medicine.anatomical_structure Integrin alpha M Spectrophotometry 030220 oncology & carcinogenesis Collagen-induced arthritis Female Collagen Lymph musculoskeletal diseases medicine.medical_specialty monocytes' plasticity Immunology Biology Bone resorption 03 medical and health sciences Sex Factors Phagocytosis Osteoclast Internal medicine Sex differences Cell Adhesion medicine Animals Cell Lineage Inflammation Macrophages Monocyte medicine.disease Arthritis Experimental Rats Disease Models Animal 030104 developmental biology Endocrinology Oxidative stress biology.protein CCR2 |
Zdroj: | Inflammation |
ISSN: | 1573-2576 0360-3997 |
Popis: | Monocytes' plasticity has an important role in the development of rheumatoid arthritis (RA), an autoimmune disease exhibiting greater prevalence in women. Contribution of this phenomenon to sex bias in RA severity was investigated in rat collagen-induced arthritis (CIA) model of RA. The greater severity of CIA in females (exhibiting signs of bone resorption) was accompanied by the higher blood level of advanced oxidation protein products and a more pro-oxidant profile. Consistently, in females, the greater density of giant multinuclear cells (monocytes/macrophages and osteoclasts) in inflamed joint tissue was found. This correlated with the higher frequencies of CCR2- and CX3CR1- expressing cells (precursors of inflammatory monocytes/macrophages and osteoclasts) among CD11b+ splenocytes. This in conjunction with the enhanced migratory capacity of CD11b+ monocytic cells in females compared with males could be linked with the higher frequencies of CCR2+CX3CR1-CD43(low)CD11b+ and CCR2-CX3CR1+CD43(hi)CD11b+ cells (corresponding to "classical" and "non-classical" monocytes, respectively) and the greater density of CD68+ cells (monocytes/macrophages and osteoclast precursors/osteoclasts) in blood and inflamed paws from female rats, respectively. Consistently, the higher levels of GM-CSF, TNF-alpha and IL-6, IL-1 beta (driving Th17 cell differentiation), and IL-17 followed by the lower level of IL-10 were measured in inflamed paw cultures from female compared with male rats. To the greater IL-17 production (associated with enhanced monocyte immigration and differentiation into osteoclasts) most likely contributed augmented Th17 cell generation in the lymph nodes draining arthritic joints from female compared with male rats. Overall, the study suggests the sex-specific contribution of monocytic lineage cells to CIA, and possibly RA development. |
Databáze: | OpenAIRE |
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