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Interleukin-18 increases TLR4 and mannose receptor expression and modulates cytokine production in human monocytes.

Dias-Melicio LA, Fernandes RK, Rodrigues DR, Golim MA, Soares AM - Mediators Inflamm. (2015)

Bottom Line: This cytokine exerts many unique biological and immunological effects.IL-18 treatment was able to increase TLR4 and MR expression by monocytes.However, IL-18 was unable to induce neither IL-12 nor IL-15 production by these cells.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Patologia, Faculdade de Medicina, Universidade Estadual Paulista (UNESP), Campus Botucatu, 18618-970 Botucatu, SP, Brazil.

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.

No MeSH data available.


Related in: MedlinePlus

TLR2, TLR4 and MR expression in CD14+ monocytes. CD14+ monocytes (column (a)) were treated with IL-18 (100 ng/mL) (column (b)), or IL-18 (100 ng/mL) plus anti-IL-18 (0,5 μg/mL) (column (c)), for 18 hours and evaluated by flow cytometry. Box-and-whisker plot showing data distribution of 15 healthy subjects tested for TLR2 (d), TLR4 (e), and MR (f). Horizontal lines represent the median values; boxes represent the 25th to 75th percentiles and vertical lines the 10th to 90th percentiles. *Statistical significance between groups is indicated (P < 0.05  × other groups).
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fig1: TLR2, TLR4 and MR expression in CD14+ monocytes. CD14+ monocytes (column (a)) were treated with IL-18 (100 ng/mL) (column (b)), or IL-18 (100 ng/mL) plus anti-IL-18 (0,5 μg/mL) (column (c)), for 18 hours and evaluated by flow cytometry. Box-and-whisker plot showing data distribution of 15 healthy subjects tested for TLR2 (d), TLR4 (e), and MR (f). Horizontal lines represent the median values; boxes represent the 25th to 75th percentiles and vertical lines the 10th to 90th percentiles. *Statistical significance between groups is indicated (P < 0.05  × other groups).

Mentions: To better understand the role of IL-18 in the expression of TLR2, TLR4, and MR by purified CD14+ monocytes, cells were treated with IL-18 and subsequently analyzed by flow cytometry. The results showed that IL-18 was able to increase TLR4 and MR expression by CD14+ monocytes (Figure 1). However, the cytokine treatment did not affect TLR2 expression (Figure 1(d)). The blocking of IL-18 with specific neutralizing antibody showed a reversal on the TLR4 and MR expression results, as shown in Figures 1(e) and 1(f). The treatment with negative isotype control did not affect the response of monocytes (data not shown). These are new data that support the autocrine role of IL-18 by identifying an important direct modulation of TLR4 and MR on human monocytes by this cytokine, seeing that purified human monocytes treated with this cytokine presented higher expression of TLR4 and MR than control cells, whereas the blocking of IL-18 with anti-IL18 reversed this effect.


Interleukin-18 increases TLR4 and mannose receptor expression and modulates cytokine production in human monocytes.

Dias-Melicio LA, Fernandes RK, Rodrigues DR, Golim MA, Soares AM - Mediators Inflamm. (2015)

TLR2, TLR4 and MR expression in CD14+ monocytes. CD14+ monocytes (column (a)) were treated with IL-18 (100 ng/mL) (column (b)), or IL-18 (100 ng/mL) plus anti-IL-18 (0,5 μg/mL) (column (c)), for 18 hours and evaluated by flow cytometry. Box-and-whisker plot showing data distribution of 15 healthy subjects tested for TLR2 (d), TLR4 (e), and MR (f). Horizontal lines represent the median values; boxes represent the 25th to 75th percentiles and vertical lines the 10th to 90th percentiles. *Statistical significance between groups is indicated (P < 0.05  × other groups).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4383410&req=5

fig1: TLR2, TLR4 and MR expression in CD14+ monocytes. CD14+ monocytes (column (a)) were treated with IL-18 (100 ng/mL) (column (b)), or IL-18 (100 ng/mL) plus anti-IL-18 (0,5 μg/mL) (column (c)), for 18 hours and evaluated by flow cytometry. Box-and-whisker plot showing data distribution of 15 healthy subjects tested for TLR2 (d), TLR4 (e), and MR (f). Horizontal lines represent the median values; boxes represent the 25th to 75th percentiles and vertical lines the 10th to 90th percentiles. *Statistical significance between groups is indicated (P < 0.05  × other groups).
Mentions: To better understand the role of IL-18 in the expression of TLR2, TLR4, and MR by purified CD14+ monocytes, cells were treated with IL-18 and subsequently analyzed by flow cytometry. The results showed that IL-18 was able to increase TLR4 and MR expression by CD14+ monocytes (Figure 1). However, the cytokine treatment did not affect TLR2 expression (Figure 1(d)). The blocking of IL-18 with specific neutralizing antibody showed a reversal on the TLR4 and MR expression results, as shown in Figures 1(e) and 1(f). The treatment with negative isotype control did not affect the response of monocytes (data not shown). These are new data that support the autocrine role of IL-18 by identifying an important direct modulation of TLR4 and MR on human monocytes by this cytokine, seeing that purified human monocytes treated with this cytokine presented higher expression of TLR4 and MR than control cells, whereas the blocking of IL-18 with anti-IL18 reversed this effect.

Bottom Line: This cytokine exerts many unique biological and immunological effects.IL-18 treatment was able to increase TLR4 and MR expression by monocytes.However, IL-18 was unable to induce neither IL-12 nor IL-15 production by these cells.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Patologia, Faculdade de Medicina, Universidade Estadual Paulista (UNESP), Campus Botucatu, 18618-970 Botucatu, SP, Brazil.

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.

No MeSH data available.


Related in: MedlinePlus