Higher TNFα responses in young males compared to females are associated with attenuation of monocyte adenylyl cyclase expression

Risøe, Petter Kirkeby; Rutkovskiy, Arkady; Ågren, Joanna; Kolseth, Ingrid Benedicte Moss; Se, Kjeldsen; Valen, Guro; Vaage, Jarle; Dahle, Maria K.

doi:10.1016/j.humimm.2015.03.018

Cited by 12 publications

(4 citation statements)

References 30 publications

(34 reference statements)

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“… 29 ADCY9 has been shown to mediate different functions of immune cells and to modulate inflammatory responses. 30 – 32 Thus, the differential mRNA expression of ADCY9 in white blood cells (most likely accounting for changes in whole blood) supports the genotype-dependent effects on inflammation responses observed in this study. Given the known interplay of inflammation and HDL functions, the above-described ADCY9 expression data also support the genotype-dependent effects on cholesterol efflux.…”

Section: Discussionsupporting

confidence: 79%

Genotype-Dependent Effects of Dalcetrapib on Cholesterol Efflux and Inflammation

Tardif

Rhainds

Brodeur

et al. 2016

Circ Cardiovasc Genet

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Section: Discussionsupporting

confidence: 79%

Genotype-Dependent Effects of Dalcetrapib on Cholesterol Efflux and Inflammation

Tardif

Rhainds

Brodeur

et al. 2016

Circ Cardiovasc Genet

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“…Indeed, myeloid-specific Adcy7 knockout mice (constitutive knockouts die in utero) show higher stimulus-induced production of TNFα by macrophages, impairment in B cell function and T cell memory, an increased susceptibility to LPS-induced endotoxic shock, and a prolonged inflammatory response36,37. In human THP-1 (monocyte-like) cells, siRNA knockdown of ADCY7 also leads to increased TNFα production 38. p.Asp439Glu affects a highly conserved amino acid in a long cytoplasmic domain immediately downstream of the first of two active sites and may affect the assembly of the active enzyme through misalignment of the active sites39.…”

Section: Resultsmentioning

confidence: 99%

Exploring the genetic architecture of inflammatory bowel disease by whole-genome sequencing identifies association at ADCY7

et al. 2017

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To further resolve the genetic architecture of the inflammatory bowel diseases, ulcerative colitis and Crohn’s disease, we sequenced the whole genomes of 4,280 patients at low coverage, and compared them to 3,652 previously sequenced population controls across 73.5 million variants. We then imputed from these sequences into new and existing GWAS cohorts, and tested for association at ~12 million variants in a total of 16,432 cases and 18,843 controls. We discovered a 0.6% frequency missense variant in ADCY7 that doubles risk of ulcerative colitis. Despite good statistical power, we did not identify any other new low-frequency risk variants, and found that such variants explained little heritability. We detected a burden of very rare, damaging missense variants in known Crohn’s disease risk genes, suggesting that more comprehensive sequencing studies will continue to improve our understanding of the biology of complex diseases.

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“…Cruz and colleagues confirmed that ADCY7 is important in corticotropin releasing factor modulation of presynaptic GABA release in the central amygdala ( Cruz et al, 2011 ). In addition, inhibition of ADCY7 expression upregulates the expression of immune-related genes ( Duan et al, 2010 ; Jiang, Sternweis & Wang, 2013 ; Risøe et al, 2015 ). In the current study, the expression of ADCY7 in goat bronchial epithelial cells was downregulated following stimulation with the P. multocida strain of serotype A. Downregulation of ADCY7 may activate the GABAergic synapse pathway, potentially inducing the host immune response.…”

Section: Discussionmentioning

confidence: 99%

The mRNA and miRNA profiles of goat bronchial epithelial cells stimulated by Pasteurella multocida strains of serotype A and D

Chen

Zhang

et al. 2022

PeerJ

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Pasteurella multocida (P. multocida) is a zoonotic bacterium that predominantly colonizes the respiratory tract and lungs of a variety of farmed and wild animals, and causes severe respiratory disease. To investigate the characteristics of the host immune response induced by P. multocida strains of serotype A and D, high-throughput mRNA-Seq and miRNA-Seq were performed to analyze the changes in goat bronchial epithelial cells stimulated by these two serotypes of P. multocida for 4 h. Quantitative RT-PCR was used to validate the randomly selected genes and miRNAs. The results revealed 204 and 117 differentially expressed mRNAs (|log2(Fold-change)| ≥ 1, p-value < 0.05) in the P. multocida serotype A and D stimulated groups, respectively. Meanwhile, the number of differentially expressed miRNAs (|log2(Fold-change)| > 0.1, p-value < 0.05) were 269 and 290, respectively. GO and KEGG enrichment analyses revealed 13 GO terms (p-value < 0.05) and four KEGG pathways (p-value < 0.05) associated with immunity. In the serotype A-stimulated group, the immune-related pathways were the GABAergic synapse and Toll-like receptor signaling pathways, while in the serotype D-stimulated group, the immune-related pathways were the phagosome and B cell receptor signaling pathways. Based on the predicted results of TargetScan and miRanda, the differentially expressed mRNA–miRNA network of immune-related GO terms and KEGG pathways was constructed. According to the cell morphological changes and the significant immune-related KEGG pathways, it was speculated that the P. multocida serotype D strain-stimulated goat bronchial epithelial cells may induce a cellular immune response earlier than serotype A-stimulated cells. Our study provides valuable insight into the host immune response mechanism induced by P. multocida strains of serotype A and D.

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Higher TNFα responses in young males compared to females are associated with attenuation of monocyte adenylyl cyclase expression

Cited by 12 publications

References 30 publications

Genotype-Dependent Effects of Dalcetrapib on Cholesterol Efflux and Inflammation

Genotype-Dependent Effects of Dalcetrapib on Cholesterol Efflux and Inflammation

Exploring the genetic architecture of inflammatory bowel disease by whole-genome sequencing identifies association at ADCY7

The mRNA and miRNA profiles of goat bronchial epithelial cells stimulated by Pasteurella multocida strains of serotype A and D

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