Effectiveness of C5a aptamers in a TNBS‑induced colitis mouse model

Abstract

Abstract. The complement-activated product, complement component 5a (C5a), is a potent inflammatory peptide with a broad spectrum of functions. In vivo and in vitro studies have demonstrated that C5a serves an important role in inflammation; however, the role of C5a in the pathogenesis of inflammatory bowel disease (IBD) is not known. The purpose of the current study was to investigate the role of C5a in IBD using an experimental mouse model of colitis. Colitis was induced in mice using 2,4,6-trinitrobenzene sulfonic acid (TNBS), and C5a aptamers were subsequently administered via intraperitoneal injection. Clinical symptoms of the disease, histopathological analysis of the colon and the level of inflammatory components were examined. The symptoms of colitis, including changes in behavior, weight loss, colon damage and an increase in inflammatory cytokines, were attenuated following the treatment of mice with TNBS-induced colitis with C5a aptamers. The aptamer-treated mice exhibited a marked attenuation of colitis when compared with untreated mice, as demonstrated by the phenotypic observations, histological examinations and inflammatory cytokine levels. Colitis is characterized by an imbalance between pro-inflammatory and anti-inflammatory mediators. The results of the current study suggest that C5a may serve a critical role in inflammation in IBD. IntroductionCrohn disease (CD) and ulcerative colitis (UC) are chronic relapsing gastrointestinal disorders, two main components of inflammatory bowel disease (IBD) (1). To date, the etiology of IBD is unknown; however, various inflammatory reactions constantly stimulate the mucosal and systemic immune systems and are involved in the inflammatory cascade (2). Approximately 25% of IBD cases occur before the age of 20 years, and 4% occur in persons younger than 5 years of age (3). In the treatment of IBD, a variety of pharmacological agents that target the inflammatory process are effective in controlling disease in patients and in sustaining symptomatic remission for prolonged periods, including tumor necrosis factor blockers, probiotics and corticosteroids (4).The complement system is widely considered to function to protect the host against invading microorganisms (5). However, previous studies investigating complement system activation have demonstrated that it may serve an injurious role in the pathogenesis of a number of inflammatory and immunological diseases (6,7). Complement activation products include complement component (C) 3a, C4a, C5a and C5b-9 and the membrane attack complex. C5a is an anaphylatoxin that exhibits chemotactic activities and promotes oxidative bursts, phagocytosis and the release of granule enzymes from neutrophils, monocytes and macrophages (7).A study involving C5a knockout mice has demonstrated that C5a serves a critical role in inflammatory diseases (8). Several inflammatory diseases have been attributed to the ability of C5a to bind with high-affinity C5a receptors (9,10), including the C5a anaphylatoxin chemotactic receptor and C5L2,...

Integrating complement into the molecular pathogenesis of Hidradenitis Suppurativa

“…[20] IL-17 administration to mucosal tissue showed a dose-dependent increase in C3 expression, suggesting a self-amplification pathway between Th17 and C3. [28] Superficially, this seems to indicate that complement is significantly implicated in Th17 activation and activity, however, given the role of neutrophil-mediated cytokines and chemokines in mediating Th17 amplification loops, [22][23][24] the possibility that complement levels merely reflect the activity of neutrophils in these disorders needs to be considered. [28] Superficially, this seems to indicate that complement is significantly implicated in Th17 activation and activity, however, given the role of neutrophil-mediated cytokines and chemokines in mediating Th17 amplification loops, [22][23][24] the possibility that complement levels merely reflect the activity of neutrophils in these disorders needs to be considered.…”

Advances in Pharmaceutical Strategies Enhancing the Efficiencies of Oral Colon-Targeted Delivery Systems in Inflammatory Bowel Disease

“…Colitis is characterized by an imbalance between proinflammatory and anti-inflammatory media. Current research results show that C5a may play a key role in IBD inflammation [ 74 ].…”