Cytokine profiles, signalling pathways and effects of fluticasone propionate in respiratory syncytial virus‐infected human foetal lung fibroblasts

Abstract

To examine cytokine production in response to RSV infection, we assessed the levels of 29 cytokines released from RSV-infected human foetal lung fibroblasts. We also examined the relationships between the effects of fluticasone propionate and various signalling pathways in the cells. Twenty-four hours after infection (1MOI), RSV-infected cells released cytokines, for example proinflammatory cytokines (IL-1β, IL-6 and TNF-α), anti-inflammatory (IL-1ra), Th1 (IFN-γ, IFN-λ1a, IL-2 and IL-12), Th2 (IL-4, IL-5, IL-10 and IL-13), granulopoiesis-inducing (G-CSF and GM-CSF), eosinophil recruitment-inducing (eotaxin and RANTES) and neutrophil recruitment-inducing cytokines (IL-8, IP-10, MCP-1 and MIP-1α). Aberrant release of most was significantly suppressed by fluticasone propionate. Twelve hours after RSV infection, increased phosphorylation of Akt, p38 MAPK, ERK1/2 and IκB-α was noted. Fluticasone propionate suppressed the phosphorylation of Akt, p38 MAPK, and ERK1/2, but not IκB-α, in virus-infected cells. TLR-4 expression was unchanged in control and RSV-infected cells, and TLR-3 and RIG-I expression was not detected. The results indicate that RSV infection induces aberrant production and release of certain cytokines through these signalling pathways in human lung fibroblasts. Overproduction and imbalance of these cytokines may be associated with the pathophysiology of RSV-induced excessive and allergic inflammation.

The impact of robust memory T cell responses against respiratory syncytial virus

“…This is in agreement with previous work showing that prolonged TNF-α production promotes weight loss during an acute RSV infection (152). However, weight loss was not completely abolished by neutralization of TNF-α in FI-RSV-immunized mice, suggesting that additional proinflammatory cytokines such as IL-1α or IL-6 are induced following RSV infection (288), that may contribute to the weight loss associated with FI-RSV VED.…”

Cytokine production and signaling pathways in respiratory virus infection

“…The representative data of virus infection-associated signaling pathways is shown in Figure 4 . Briefly, a previous report showed that RSV infection in human fetal lung fibroblasts (MRC-5 cells) induces various cytokines through the activation (phosphorylation) of Akt (murine thymoma viral oncogene homolog/protein kinase B), p38MAPK (mitogen activated protein kinase), ERK1/2 (extracellular signal-regulated kinase), and IκB-α (Seki et al, 2013). Human rhinovirus (HRV) infection in human bronchial epithelium cells (BEAS-2B cells) activated p38MAPK, ERK1/2, and NF-κB (nuclear factor kappa B protein).…”

“…Numerous reports show that most respiratory virus infections can induce the production of various types of cytokines in vitro and in vivo (Khaitov et al, 2009; Koetzler et al, 2009; Martínez et al, 2009; Sharma et al, 2009; Ishioka et al, 2011; Lewis et al, 2012; Seki et al, 2013). The findings of previous in vitro studies suggest that influenza virus type A [subtype A(H1N1) virus]-infected human airway epithelial cells produces significant amounts of IL-1, IL-6, and IL-8 (Hofmann et al, 1997).…”

Induction of high-mobility group Box-1 in vitro and in vivo by respiratory syncytial virus

“…It has been previously argued that an exogenous or endogenous immunogenic stimulus will activate the innate immune system only if able to induce the release of alarmins, like HMGB1 ( 30 ). By binding to its cognate receptors, HMGB1 modifies cell functions not only with direct autocrine/paracrine activity ( 31 ), but also through indirect potentiation of other inflammatory pathways, e.g., activation of multiple pattern-recognition receptors like TLR2 and TLR4 ( 31 ); release of proinflammatory cytokines like IL-1, IL-6, and IL-8 ( 32 ); and interference with T cell responses inducing TH1 polarization ( 33 ).…”