Adiponectin Is a Component of the Inflammatory Cascade in Rheumatoid Arthritis

Abstract

Adiponectin is a secretory protein of adipocytes that plays an important role in pathological processes by participation in modulating the immune and inflammatory responses. The pro-inflammatory effect of adiponectin is observed in rheumatoid arthritis (RA). In this study, we examined adiponectin plasma levels and the expression of adiponectin in bone marrow tissue samples, synovium samples, and infrapatellar fat pad samples from patients with osteoarthritis (OA) and RA. Additionally we examined the expression of adiponectin receptors AdipoR1 and AdipoR2 in synovium samples and infrapatellar fat pad samples from patients with OA and RA. We also assessed the correlations between adiponectin plasma concentrations, adiponectin expression in bone marrow, synovium, infrapatellar fat pad, and plasma levels of selected cytokines. We found increased expression of adiponectin in synovium samples and infrapatellar fat pad samples from patients with RA as compared to patients with OA. There were no statistically significant differences of adiponectin plasma levels and adiponectin expression in bone marrow tissue samples between OA and RA patients. There were no differences in the expression of AdipoR1 and AdipoR2 at the mRNA level in synovial tissue and the infrapatellar fat pad between RA and OA patients. However, in immunohistochemical analysis in samples of the synovial membrane from RA patients, we observed very strong expression of adiponectin in intima cells, macrophages, and subintimal fibroblasts, such as synoviocytes, vs. strong expression in OA samples. Very strong expression of adiponectin was also noted in adipocytes of Hoffa’s fat pad of RA patients. Expression of AdipoR1 was stronger in RA tissue samples, while AdipoR2 expression was very similar in both RA and OA samples. Our results showed increased adiponectin expression in the synovial membrane and Hoffa’s pad in RA patients compared to that of OA patients. However, there were no differences in plasma adiponectin concentrations and its expression in bone marrow. The results suggest that adiponectin is a component of the inflammatory cascade that is present in RA. Pro-inflammatory factors enhance the expression of adiponectin, especially in joint tissues—the synovial membrane and Hoffa’s fat pad. In turn, adiponectin also increases the expression of further pro-inflammatory mediators.

Adiponectin, Leptin and Resistin in Patients with Psoriasis

“…This is explained by the stimulation of adiponectin synthesis by pro-inflammatory factors such as CRP. In our previous study, we demonstrated the stimulation of adiponectin expression in fibroblast-like synoviocytes by pro-inflammatory mediators such as TNF and LPS [ 37 ].…”

Macrophage-derived exosomal miRNA-141 triggers endothelial cell pyroptosis by targeting NLRP3 to accelerate sepsis progression

“…Macrophages are pivotal orchestrators in the pathophysiology of a myriad of chronic inflammatory disorders and autoimmune diseases. 13 – 16 It is increasingly evident that uncontrolled macrophage activation is a fundamental mechanism underlying sepsis. 20 , 21 Exhibiting remarkable phenotypic plasticity, macrophages can oscillate between pro-inflammatory M1 and anti-inflammatory M2 states in response to varying environmental cues.…”

“…Macrophages are pivotal to the immune response and represent the vanguard in defense against pathogenic incursions. 13 – 17 They exhibit a high degree of plasticity, allowing them to adapt their phenotype along a spectrum ranging from M1 pro-inflammatory to M2 anti-inflammatory states, contingent upon environmental cues. 18 The promotion of the phenotypic transition from M1 to M2 macrophages plays a crucial role in attenuating inflammatory responses, augmenting tissue repairprocesses, and enhancing regenerative capabilities.…”

Decrease in Leptin Expression in the Liver after Prolonged Every-Other-Day Feeding in C57Bl/6 Male Mice

“…In hepatocytes, ADIPOQ lowers the lipid content, including ceramides, which leads to tumor suppression in liver tissue [22]. There are data suggesting the expression of adiponectin in tissues other than adipose tissue: bone marrow, skeletal muscle, synovial membranes, cardiomyocytes, and salivary gland epithelium [8,[23][24][25]. Local ADIPOQ production's involvement in the regulation and metabolism of cardiomyocytes has been postulated [24].…”

“…Adipose tissue is a major source of ADIPOQ and leptin, but there are reports showing other local sources of these adipokines, like synovial membranes in inflammatory disorders such as rheumatoid arthritis (RA) and osteoarthritis (OA), induced liver fibrosis, or pregnancy [23,34,39]. There are also reports showing changes in the expression of adipokines and their receptors in plasma, adipose tissue, and tumors after CR regimes [4,[11][12][13]15,38].…”