Interleukin‐18 Increases TLR4 and Mannose Receptor Expression and Modulates Cytokine Production in Human Monocytes

Abstract

Interleukin-18 is a proinflammatory cytokine belonging to the interleukin-1 family of cytokines. This cytokine exerts many unique biological and immunological effects. To explore the role of IL-18 in inflammatory innate immune responses, we investigated its impact on expression of two toll-like receptors (TLR2 and TLR4) and mannose receptor (MR) by human peripheral blood monocytes and its effect on TNF-α, IL-12, IL-15, and IL-10 production. Monocytes from healthy donors were stimulated or not with IL-18 for 18 h, and then the TLR2, TLR4, and MR expression and intracellular TNF-α, IL-12, and IL-10 production were assessed by flow cytometry and the levels of TNF-α, IL-12, IL-15, and IL-10 in culture supernatants were measured by ELISA. IL-18 treatment was able to increase TLR4 and MR expression by monocytes. The production of TNF-α and IL-10 was also increased by cytokine treatment. However, IL-18 was unable to induce neither IL-12 nor IL-15 production by these cells. Taken together, these results show an important role of IL-18 on the early phase of inflammatory response by promoting the expression of some pattern recognition receptors (PRRs) that are important during the microbe recognition phase and by inducing some important cytokines such as TNF-α and IL-10.

NLRP6 function in inflammatory monocytes reduces susceptibility to chemically induced intestinal injury

“…Furthermore, both Il18 −/− and Il18r1 −/− monocytes isolated from DSS-treated mice have impaired production of TNFα similar to that observed with Nlrp6 −/− monocytes, consistent with a role for NLPR6 in regulating TNFα production in monocytes via IL-18. Although IL-18 is typically associated with the upregulation of Th1 responses, and in particular, IFNγ, 40 IL-18 has also been shown to activate monocytes to enhance TNFα production, 41, 42 consistent with our data.…”

Prokaryotic Expression and Anti-IBDV Activity of Chicken Interleukin-18 and Interferon-γ

“…AY775780.1). Bam HI and Hin dIII sites were added at the 5 ′ and 3 ′ ends of the ChIL-18 gene primers, respectively [Dias-Melicio et al, 2015]. The ChIFN-γ gene was cloned from the total RNA of chicken spleen cells following PCR amplification with the primers 5 ′ -CCCAAGCTTTCATAGGTTGTGCCTTTCAT-3 ′ and 5 ′ -CC-CAAGCTTTAGCAATTGCATCTCCTCTG-3 ′ , which were designed according to the IFN-γ sequence (GenBank accession No.…”

Nutritional modulation of gut microbiota — the impact on metabolic disease pathophysiology

“…Thus, modulating CD14 and TLR signaling can drastically alter inflammatory responses leading to a decrease in tissue macrophage infiltration and pro-inflammatory cytokine expression [35]. These immune-mediated responses impact the pro-inflammatory milieu that maintains inflammatory insults and adversely impacts host metabolism [36]. Together, these data suggest that manipulation of the microbial community by shifting abundances and proportions of specific microbes may provide an avenue for treating NAFLD.…”

“…Several reviews detail the mechanisms involved in adipose tissue inflammation and insulin resistance [41, 47, 48]. Overall, these studies indicate that early inflammatory responses in obesity and metabolic syndrome are driven by nutritional intake, postprandial metabolic regulation, and microbe recognition phases that promote microbial-induced immune signaling pathways [36]. Immune-mediated signaling involved in excess dietary lipid intake and microbial dysbiosis are associated with multiple inflammatory-related complications including: insulin resistance, pancreatic beta cell dysfunction, NAFLD, and cardiovascular inflammation [47, 49–51].…”