Complement regulation in tenocytes under the influence of leukocytes in an indirect co-culture model

Complement Regulation in Human Tenocytes under the Influence of Anaphylatoxin C5a

“…In addition, TNFα is known to be increased in the case of tendon pathology [4]. We know that C5aR gene expression is elevated in tenocytes in response to TNFα stimulation in an intermediate stage (4 h) of inflammation [10]. Conversely, in our present study, we could show that C5a suppresses the TNFα gene expression in these cells in an early phase of 0.5 h in comparison to the control group ( Figure 4A).…”

“…These immune cells are actively involved in producing proinflammatory cytokines, such as TNFα, interleukin (IL)-6, IL-1β, etc., in addition to complement factors that can trigger the inflammation process [1,9]. A direct TNFα stimulation of tenocytes and an indirect co-culture with leukocyte subpopulations, peripheral blood mononuclear cells, and neutrophils have been studied in our previous in vitro study to understand the complement response in tenocytes [10].…”

“…TNFα and other pro-inflammatory mediators often accompany an increase in complement and can regulate each other in an inflammatory process [10,18,19]. Even though various cytokines have been discussed in the research field of tendon inflammation [20,21], IL-1β, TNFα, IL-6, and IL-10 are considered in various studies as the key cytokines in tendon diseases, as reported in a systematic review [9].…”

“…Even though various cytokines have been discussed in the research field of tendon inflammation [20,21], IL-1β, TNFα, IL-6, and IL-10 are considered in various studies as the key cytokines in tendon diseases, as reported in a systematic review [9]. The complement system attracts increasing attention in this tendon research since complement factors and receptors could be detected in tenocytes and their regulation in-vitro in response to physical and biochemical influences [10,18,19]. Therefore, more research has to be performed to understand the role of complement factors as possible players in the pathogenesis of tendinopathy.…”

Animal model for tendinopathy

“…Tendon cells play a key role in maintaining the balance between ECM synthesis and decomposition through synthesizing Col, proteoglycans and elastic proteins or producing matrix MMPs and elastases [ 36 ]. Immune cells (e.g., neutrophils and macrophages) are also involved in this process by producing degrading enzymes [ 37 ]. ECM, in turn, regulates the function of tendon and immune cells.…”