Effect of interleukin-6, -17, -21, -22, and -23 and STAT3 on signal transduction pathways and their inhibition in autoimmune arthritis

Abstract

Rheumatic diseases are complex autoimmune diseases which include among others rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), and psoriatic arthritis (PsA). These diseases are characterized by prolonged and increased secretion of inflammatory factors, eventually leading to inflammation. This is often accompanied by persistent pain and stiffness in the joint and finally bone destruction and osteoporosis. These diseases can occur at any age, regardless of gender or origin. Autoimmune arthritis is admittedly associated with long-term treatment, and discontinuation of medication is associated with unavoidable relapse. Therefore, it is important to detect the disease at an early stage and apply appropriate preventative measures. During inflammation, pro-inflammatory factors such as interleukins (IL)-6, -17, -21, -22, and -23 are secreted, while anti-inflammatory factors including IL-10 are downregulated. Research conducted over the past several years has focused on inhibiting inflammatory pathways and activating anti-inflammatory factors to improve the quality of life of people with rheumatic diseases. The aim of this paper is to review current knowledge on stimulatory and inhibitory pathways involving the signal transducer and activator of transcription 3 (STAT3). STAT3 has been shown to be one of the crucial factors involved in inflammation and is directly linked with other pro-inflammatory factors and thus is a target of current research on rheumatoid diseases.

Zerumbone Protects Rats from Collagen-Induced Arthritis by Inhibiting Oxidative Outbursts and Inflammatory Cytokine Levels

“… 74 − 79 NF-κB is a key player in RA that initiates and exacerbates inflammation. 80 − 82 At the disease site, TNF-α triggers the synthesis of IL-6 and IL-1β by macrophages that further facilitates leukocyte infiltration and vasodilation. 82 In this study, IL-10 levels were significantly increased in CIA animals compared to healthy ones, but the exact mechanisms of elevated release of this anti-inflammatory cytokine remain unclear.…”

Molecular mechanisms of the development of the phenomena of peripheral and central sensitization in rheumatoid arthritis

“…Существуют две формы ИЛ-1 -ИЛ-1α, представленный в виде молекулы, которая способна проводить сигнал, будучи связана с мембраной, и ИЛ-1β, действие которого возможно только после перехода в активную растворимую форму посредством взаимодействия с каспазой 1 (ICE). Обе формы связываются с одним рецептором (ИЛ-1-Р1) и далее взаимодействуют с белком ИЛ-1 RAcP (ко-рецептром), осуществляющим передачу провоспалительного сигнала [51,52].…”

NKG2D receptor regulates CD4 + T cell differentiation via interaction with dendritic cells in patients with juvenile idiopathic arthritis

“…There are at least three major onset types of JIA: pauciarticular, polyarticular, and systemic. CD4 + T cells are important in the initiation and propagation of JIA, leading to recruitment of innate and adaptive immune cells and the production of inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-17, and interferon-gamma (IFN γ), which collectively lead to chronic inflammation [1]. The activation of CD4 + T cells depends on the interaction with antigen present cells.…”