IL-1β Expression In Macrophages Research Articles

Cortisol response and immune-related effects of Atlantic salmon ( Salmo salar Linnaeus) subjected to short- and long-term stress

It is generally considered that stress causes decreased immune function in fish. In this study we examined in Atlantic salmon ( Salmo salar Linnaeus) the effects of both short- (a single 15 s out of water) and long-term (4 weeks of daily handling 15 s out of water) stress on plasma cortisol (free and total) and glucose levels, expression of interleukin-1β (IL-1β) and survival of head kidney (HK) macrophages under culture with Aeromonas salmonicida. In the short-term study, samples were collected prior to the application of the stressor, and at 1, 3, 6, 12 and 24 h post stress. Free and total plasma cortisol levels and the percentage of free cortisol increased significantly in the stressed group at 1 and 3 h post stress. Plasma glucose levels were significantly higher than those of control fish at 1, 3 and 6 h post stress. Constitutive expression of IL-1β in macrophages isolated from head kidneys in stressed fish was significantly higher at 1 and 3 h post stress. However, lipopolysaccharide (LPS) stimulated expression of IL-1β in HK macrophages, exhibited significantly higher fold increases in unstressed fish compared to stressed fish. In the long-term study, with the exception of an increase in plasma glucose levels at 1 week, there were no significant differences in stress parameters between groups. There was a significantly higher constitutive IL-1β expression in macrophages isolated from stressed fish over the first 2 weeks. At weeks 1, 2 and 3 the magnitude of IL-1β response of isolated HK macrophages to LPS stimulation was reduced in >90% of the stressed fish. At 4 weeks there was no significant difference in inducible IL-1β expression between the groups. Macrophages isolated from stressed fish also showed significantly decreased survival when exposed to A. salmonicida. This study shows a clear pattern from repeated handling stress, whereby effects on immune cells begin with increased constitutive expression of IL-1β, followed by decreased stimulation of leucocytes by extracellular antigen, and finally decreased leukocyte survival when exposed to A. salmonicida. The implications of these changes in the immune system will be discussed with respect to the use of classical indicators of stress to predict possible effects on the immune system of fish.

2-Acetylaminofluorene inhibits interleukin-1β production in LPS-stimulated macrophages by blocking NF-κB/Rel activation

In the present study, we demonstrate the inhibitory effect of 2-acetylaminofluorene (AAF) on interleukin-1β (IL-1β) gene expression in lipopolysaccharide (LPS)-stimulated macrophages. Acetylaminofluorene inhibited IL-1 production in LPS-stimulated splenic macrophages and RAW 264.7 cells. Additionally, AAF also suppressed LPS-induced mRNA expression of IL-1β in macrophages. To further characterize the molecular mechanism responsible for AAF-mediated suppression of IL-1β, we investigated the effect of AAF on LPS-mediated activation of transcription factors, such as NF-κB, AP-1, CRE and NF-IL6, which are known to be important for LPS-induced gene expression of IL-1β. Treatment of AAF caused a dose-related inhibition of LPS-induced NF-κB/Rel transcriptional activation, while the transcriptional activation of AP-1, CRE and NF-IL6 was not affected by AAF. Furthermore, LPS-induced NF-κB/Rel DNA binding was also suppressed by AAF treatment. These results suggest that AAF inhibits IL-1β gene expression by blocking NF-κB/Rel activation.

Differential regulation of macrophage interleukin-1 (IL-1), IL-12, and CD80-CD86 by two bacterial toxins.

The ability of innate immune cells to differentially respond to various bacterial components provides a mechanism by which the acquired immune response may be tailored to specific pathogens. The response of innate immune cells to bacterial components provides regulatory signals to cognate immune cells. These signals include secreted cytokines and costimulatory molecules, and to a large extent they determine the quantitative and qualitative nature of the immune response. In order to determine if innate immune cells can differentially respond to bacterial components, we compared the responses of macrophages to two bacterially derived molecules, cholera toxin (CT) and lipopolysaccharide (LPS). We found that CT and LPS differentially regulated the expression of interleukin-12 (IL-12) and CD80-CD86 but not that of IL-1beta. LPS and CT each induced IL-1beta expression in macrophages, while only LPS induced IL-12 and only CT induced CD80-CD86. These differences were markedly potentiated in gamma interferon (IFN-gamma)-treated macrophages, in which LPS potently induced IL-12 and CD80-CD86 expression. In contrast, IFN-gamma treatment had no effect on the expression of IL-1beta. These results define a molecular basis for the differential pathogenicities of bacterial toxins and are relevant to the design of vaccine adjuvants able to selectively induce desired types of immunity.