Different Secretory Activity of Articular and Subcutaneous Adipose Tissues from Rheumatoid Arthritis and Osteoarthritis Patients

Abstract

Rheumatoid arthritis (RA) and osteoarthritis (OA) are characterized by joint and systemic high- or low-grade inflammation, respectively. Adipose tissue (AT) may contribute to the pathogenesis of these diseases. To address this issue, we investigated whether basal and pro-inflammatory cytokine (IL-1β)-triggered release of adipocytokines (TNF, IL-6, IL-10, IL-1Ra, TGFβ, CCL2/MCP-1, CCL5/RANTES, MMP-3) from subcutaneous (ScAT) and intraarticular (AAT) adipose tissues of RA and OA patients mirror differences between these diseases in an intensity of systemic and local inflammation. We found that in both diseases basal adipocytokine release was usually higher from AAT than ScAT, reflecting stronger local than systemic inflammation. However, ScAT secreted considerable amounts of pro- and anti-inflammatory factors as well. Spontaneous secretion of some adipocytokines (MMP-3 and/or TNF, CCL2/MCP-1, IL-1Ra) was higher in osteoarthritis than rheumatoid ATs and probably caused by weaker anti-inflammatory treatment of OA patients. By contrast, reactivity of ATs to IL-1β was significantly lower in OA than RA and IL-1β antagonist (IL-1Ra) could be responsible for this because we found its overproduction in OA ATs. Interestingly, higher reactivity of ScAT than AAT to IL-1β was a characteristic for OA while reactivity of rheumatoid ScAT and AAT to this stimulus was equal. We conclude that differences between OA and RA in reactivity of AAT and ScAT to pro-inflammatory stimulus mimicking in vivo condition reflect dissimilarity in an intensity of disease-specific inflammation and thus support contribution of ATs to these pathological processes. Moreover, we propose that more efficient anti-inflammatory mechanism(s) are preserved in ATs of OA than RA patients.

Keywords: articular adipose tissue; chemokines; cytokines; osteoarthritis; rheumatoid arthritis; subcutaneous adipose tissue.

Fig. 1.

Basal secretion of proinflammatory cytokines and chemokines by articular (AAT) and subcutaneous (ScAT) adipose tissues obtained from osteoarthritis (OA) and rheumatoid arthritis (RA) patients. Tissues were cultured for 24 h in culture medium. Concentrations of proinflammatory cytokines (IL-6, TNF), chemokines (CCL2/MCP-1, CCL5/RANTES) and metalloproteinase (MMP-3) were measured in culture supernatants by specific ELISAs. Data are expressed as the level of adipo(cyto)kine production by 100 mg tissue and presented in pairs of tissues obtained from the same patient. Statistically significant differences between AAT and ScAT are shown (*p ≤ 0,05; **p ≤ 0,01). TNF tumor necrosis factor; IL interleukin; CCL2/MCP-1 C-C motif chemokine ligand 2/monocyte chemoattractant protein 1; CCL5/RANTES C-C motif chemokine ligand 5/regulated on activation, Normal T cell expressed and secreted; MMP-3 matrix metalloproteinase-3.

Fig. 2

Basal secretion of anti-inflammatory cytokines by articular (AAT) and subcutaneous (ScAT) adipose tissues obtained from osteoarthritis (OA) and rheumatoid arthritis (RA) patients. Tissues were cultured for 24 h in culture medium. Concentrations of anti-inflammatory cytokines (IL-1Ra, IL-10, TGFβ) were measured in culture supernatants by specific ELISAs. Data are expressed as the level of cytokine production by 100 mg tissue and presented in pairs of tissues obtained from the same patient. Statistically significant differences between AAT and ScAT are shown (*p ≤ 0.05; **p ≤ 0.01). IL interleukin; IL-1Ra interleukin 1 receptor antagonist; TGFβ transforming growth factor beta.

Fig. 3.

Reactivity of articular (AAT) and subcutaneous (ScAT) adipose tissues from osteoarthritis (OA) and rheumatoid arthritis (RA) patients to proinflammatory stimulus- secretion of proinflammatory cytokines (IL-6, TNF), chemokines (CCL2/MCP-1, CCL5/RANTES) and metalloproteinase MMP-3. Tissues were cultured for 24 h in culture medium alone (control) or in the presence of human recombinant IL-1β (1 ng/ml). Concentrations of tested adipocytokines were measured in culture supernatants by specific ELISAs. Effect of IL-1β stimulation was analyzed as stimulation to control ratio (IS, index of stimulation). Statistically significant differences between AAT and ScAT are shown (*p ≤ 0.05; **p ≤ 0.01); other explanations as in Fig. 1.

Fig. 4

Reactivity of articular (AAT) and subcutaneous (ScAT) adipose tissues from osteoarthritis (OA) and rheumatoid arthritis (RA) patients to proinflammatory stimulus- secretion of anti-inflammatory cytokines (IL-1Ra, IL-10, TGFβ). Tissues were cultured for 24 h in culture medium alone (control) or in the presence of human recombinant IL-1β (1 ng/ml). Concentrations of tested cytokines were measured in culture supernatants by specific ELISAs. Effect of IL-1β stimulation was analyzed as stimulation to control ratio (IS, index of stimulation). Statistically significant differences between AAT and ScAT are shown (*p ≤ 0.05; **p ≤ 0.01); other explanations as in Fig. 2.