Steroids induce a disequilibrium of secreted interleukin-1 receptor antagonist and interleukin-1  synthesis by human neutrophils

Langereis, Jeroen D.; Oudijk, Erik-Jan; Schweizer, René C.; Lammers, J.-W. J.; Koenderman, Leo; Ulfman, Laurien H.

doi:10.1183/09031936.00170409

Cited by 31 publications

(26 citation statements)

References 64 publications

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“…We measured total ex vivo IL-1Ra and IL-1β production following four hours of whole blood incubation with LPS, which aimed to mimic the in vivo conditions of a bacterially-induced inflammatory immune response while minimizing participant risk. Consistent with previous reports among pregnant and nonpregnant samples, IL-1Ra and IL-1β production covaried (Heng et al, 2014; Langereis et al, 2011). However, inhibition of IL-1β by IL-1Ra during the inflammatory immune response appeared to be compromised among women with GG genotype, which is important considering that greater IL-1β production went on to predict earlier birth.…”

Section: Discussionsupporting

confidence: 91%

Interleukin-1 Receptor Antagonist Polymorphism and Birth Timing

et al. 2017

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Background Timing of birth is a major determinant of newborn health. African American women are at increased risk for early birth, particularly via the inflammatory pathway. Variants of the IL1RN) gene, which encode the interleukin-1 receptor antagonist (IL-1Ra) protein, are implicated in early birth. The biological pathways linking these variables remain unclear. Evidence also suggests inflammatory pathways differ by race; however, studies among African American women are lacking. Objectives We assessed whether an IL1RN variant was associated with timing of birth among African American women and whether this relationship was mediated by lower anti-inflammatory IL-1Ra production or related to a decrease in inhibition of proinflammatory IL-1β production. Methods A candidate gene study using a prospective cohort design was used. We collected blood samples at 28–32 weeks gestation among African American women experiencing an uncomplicated pregnancy (N = 89). IL1RN SNP rs2637988 was genotyped and lipopolysaccharide-stimulated IL-1Ra and IL-1β production quantified. Medical record review determined timing of birth. Results Women with GG genotype gave birth earlier than women with AA/AG genotypes (b* = 0.21, p = .04). There was no indirect effect of IL1RN SNP rs2637988 allele status on timing of birth through IL-1Ra production, as evidenced by a nonsignificant product of coefficients in mediational analyses (ab = .006, 95% CI [-0.05, 0.13]. Women with GG genotype demonstrated less inhibition of IL-1β production for a unit positive difference in IL-1Ra production than women with AA/AG genotypes (b* = 0.93, p = .03). Greater IL-1β production at 28–32 weeks of pregnancy was marginally associated with earlier birth (b* = 0.21, p = .05). Discussion Women with GG genotype may be at risk for earlier birth due to diminished IL-1β inhibition, allowing for initiation of a robust inflammatory response upon even mild immune challenge. Study of inflammatory contributions to early birth among African American women may be key to identifying potential prognostic markers of risk and targeted preventive interventions.

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Section: Discussionsupporting

confidence: 91%

Interleukin-1 Receptor Antagonist Polymorphism and Birth Timing

et al. 2017

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“…Although IL-1␤ binds to interleukin receptor 1 to induce proinflammatory signaling in the cell, IL-1RA competes with IL-1␤, acting as an anti-inflammatory effector that counter-regulates the pro-inflammatory cascade. The ratio of IL-1␤ to IL-1RA determines whether the final signal becomes pro-or anti-inflammatory (38). In activated NHDF, most of the upregulated IL-1␤ was found retained inside the cells and, interestingly, IL-1RA was up-regulated only in the cytoplasm but not secreted (Fig.…”

Section: Discussionmentioning

confidence: 98%

Contribution of Human Fibroblasts and Endothelial Cells to the Hallmarks of Inflammation as Determined by Proteome Profiling

Slany

Bileck

Kreutz

et al. 2016

Molecular & Cellular Proteomics

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In order to systematically analyze proteins fulfilling effector functionalities during inflammation, here we present a comprehensive proteome study of inflammatory activated primary human endothelial cells and fibroblasts. Cells were stimulated with interleukin 1-␤ and fractionated in order to obtain secreted, cytoplasmic and nuclear protein fractions. Proteins were submitted to a data-dependent bottom up analytical platform using a QExactive orbitrap and the MaxQuant software for protein identification and label-free quantification. Results were further combined with similarly generated data previously obtained from the analysis of inflammatory activated peripheral blood mononuclear cells. Applying a false discovery rate of less than 0.01 at both, peptide and protein level, a total of 8370 protein groups assembled from 117,599 peptides was identified; mass spectrometry data have been made fully accessible via ProteomeXchange with identifier PXD003406 to PXD003417. Comparative proteome analysis allowed us to determine common and cell type-specific inflammation signatures comprising novel candidate marker molecules and related expression patterns of transcription factors. Cardinal features of inflammation such as interleukin 1-␤ processing and the interferon response differed substantially between the investigated cells. Furthermore, cells also exerted similar inflammation-related tasks; however, by making use of different sets of proteins. Hallmarks of inflammation thus emerged, including angiogenesis, extracellular matrix reorganization, adaptive and innate immune responses, oxidative stress response, cell proliferation and differentiation, cell adhesion and migration in addition to monosaccharide metabolic processes, representing both, common and cell type-specific responsibilities of cells during inflammation. Molecular & Cellular

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“…[6][7][8] For example, steroids are known to suppress interleukin-1beta (IL-1B) expression in various cell types. [9][10][11] Since there is a significant body of literature that clearly indicates that cytokine and growth factor networks are critical to controlling inflammation and wound healing, it is likely that cytokine networks play a significant role in controlling inflammation and wound healing that impact sensor function in vivo.…”

Section: Introductionmentioning

confidence: 99%