Increased Toll-Like Receptor 2 Expression in Peptidoglycan-Treated Blood Monocytes Is Associated with Insulin Resistance in Patients with Nondiabetic Rheumatoid Arthritis
The close relationship between increased TLR-2 expression in blood monocytes and insulin resistance in RA patients is shown in this study. Traditional risk factors for metabolic disorders, including the waist circumstance, body mass index (BMI), triglyceride (TG), and ratio of TG to high density lipoprotein (HDL) cholesterol, were closely correlated with HOMA (homoeostasis model assessment) index in patients with nondiabetic RA. Expressions of TLR2 in peripheral blood monocytes, following stimulation with peptidoglycan which is known as a TLR2 agonist, were closely correlated with the HOMA index, TNF-α, and IL-6 concentrations. Accordingly, TLR-2 receptor and its related inflammatory cytokines could be potential therapeutic targets in managing insulin resistance in RA patients. 1. Introduction Rheumatoid arthritis (RA) is a complex disease whose pathogenesis remains unknown. Patients with RA have systemic inflammation, as well as increased morbidity and mortality from cardiovascular disease [1, 2]. Various risk factors have been identified that contribute to atherosclerosis in RA patients [3, 4]. Insulin resistance is the most important of these risk factors. Recent years have seen increased attention devoted to inflammation associated insulin resistance [5]. Increasing numbers of research studies illuminate several possible mechanisms, including activation of innate system. Toll-like receptors (TLRs), as key molecular components of the innate immune system, are of a central interest in innate system associated insulin resistance. Twelve members of TLRs have been identified in mammals [6]. The predominant site of TLRs expression is on cells of the innate system, particularly on monocytes [7]. Monocytes are involved in inflammation and the development of insulin resistance [8–10]. The TLRs recognize numerous ligands; for example, TLR2 and TLR4 were hypothesized to recognize components of the bacterial cell wall such as peptidoglycan and lipopolysaccharide, respectively, and to interact with lipid-containing molecules [11]. TLRs participate in the pathogenesis of insulin resistance in animal models [12, 13] and mediate vascular inflammation and insulin resistance in diet-induced obesity [14]. Additionally, TLRs can link innate immunity and fatty acid-induced insulin resistance [12]. Activation of TLRs in adipocyte has been implicated in the onset of insulin resistance in obesity and type-2 diabetes [15]. Raised TLR expression and signaling were also observed in muscles of insulin resistant individuals [16]. High glucose can induce TLR2 and TLR4
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