Antimicrobial peptides modulate lipopolysaccharide-induced gene expression of cytokines IL1β and IL10 and toll-like receptor 4 in rat blood leukocytes

Abstract

INTRODUCTION: Inflammation is a common pathological condition. On the one hand, inflammation plays a protective role, without it dangerous local processes would remain unrecognized. On the other hand, a cytokine storm can develop under conditions of systemic inflammation, which, in turn, can lead to multiple organ failure. Therefore, it is important to understand the mechanisms involved in the regulation of cytokine production in the early stages of inflammation. OBJECTIVE: The aim of this study was to evaluate the immunomodulatory properties of human defensin (HNP-1) and porcine protegrin (PG-1) antimicrobial peptides in vivo under conditions of inflammatory process initiation. METHODS: Lipopolysaccharide was administered intraperitoneally to laboratory rats to initiate an inflammatory response. Following the onset of inflammation, antimicrobial peptides were also administered intraperitoneally. The immunomodulatory effect of the peptides was evaluated by measuring the changes in gene expression of toll-like receptor 4 (TLR4) and cytokines IL1β and IL10 in the blood leukocytes of the animals using real-time PCR. RESULTS: The lipopolysaccharide-induced expression of Il1b and Il10 in leukocytes, as well as the lipopolysaccharide-induced Tlr4 expression in whole blood leukocytes and isolated mononuclear cells, was reduced to varying degrees by the introduction of HNP-1 and PG-1. CONCLUSION: It can be assumed that at the early stage of the inflammatory process, defensins can act as moderate pro-inflammatory factors, suppressing the gene expression of the anti-inflammatory cytokine IL10, but at the same time slightly reducing the gene expression of the pro-inflammatory cytokine IL1β.