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B27 modulation of LPS response

ABSTRACT: Objectives How HLA-B27 contributes towards arthritis susceptibility is still unclear, but effects on the response to bacteria unrelated to the classical antigen presenting role of B27 have been suggested. This study investigated whether HLA-B27 modulates the innate response to LPS, a component shared between all Gram –ve bacteria that can trigger reactive arthritis. Methods Pools of U937 transfectants expressing either HLA-B27, HLA-A2, or the expression plasmid alone were differentiated with PMA and stimulated with LPS. Supernatants were analysed for TNF-alpha secretion and the gene expression profiles of unstimulated and LPS stimulated cells were determined by microarray analysis. Changes in gene expression that are indicative of an unfolded protein response were also analysed by quantitative PCR. Results TNF-alpha secretion, a biological marker of the inflammatory response to LPS, was not significantly different between U937-B27 and U937-control. No differences in gene expression between unstimulated U937- B27 and U937-control lines were detected. Both U937-control and U937-B27 exhibited a stereotypic response to LPS. Only 1 gene, OAS2, was differentially expressed by these cell lines, and this was confirmed by quantitative PCR. Analysis of XBP-1 splicing suggested that a small increase in the unfolded protein response is induced following LPS stimulation, but this increase was seen in all transfectants. Conclusions The expression of B27 does not profoundly alter gene expression following LPS stimulation. Therefore, additional signals, such as those provided by cytokines or intracellular infection, may be required to reveal any influence of B27 expression on the inflammatory response. Keywords: antigen response

ORGANISM(S): Homo sapiens

PROVIDER: GSE4579 | GEO | 2006/04/10

SECONDARY ACCESSION(S): PRJNA94421

REPOSITORIES: GEO

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New insights into key genes and pathways involved in the pathogenesis of HLA-B27-associated acute anterior uveitis

Project description:HLA-B27-associated inflammatory diseases remains one of the strongest HLA-disease known to date. HLA-B27-associated acute anterior uveitis has wide-ranging medical significance due to its ocular, systemic, immunologic, and genetic features. To investigate the genes and signalling pathways located upstream of the inflammatory processes in HLA-B27-associated acute anterior uveitis will help to know the mechanism of this disease. HLA-B27-positive and -negative monocytes isolated from human peripheral blood were stimulated with Vibrio cholera lipopolysaccharide (LPS). Gene expression microarrays were used to identify the differentially expressed genes, and they were analysed by a series of bioinformatics-based techniques. Gene expression microarray analysis revealed marked differences between B27-positive monocytes in the genes that are upregulated in response to LPS stimulation. Gene Ontology enrichment (GO) and pathway analysis indicated that genes participating in protein transport and folding were essential to the inflammatory process. The LPS receptor, TLR4, induced the Toll-like receptor signalling pathway and pathways related to Vibrio cholerae infection, which are located upstream of the network and contribute to the overall response. Among the DE genes, PIK3CA, PIK3CB, AKT3, and MAPK1 may play critical roles in inflammation.Equivalent LPS stimulation induces a different response in HLA-B27-positive monocytes compared to monocytes lacking this HLA protein, suggesting that the TLR pathway is involved in the pathogenesis of HLA-B27-associated AAU. Blocking this pathway and other pathways by siRNA interference of candidate genes may contribute to the development of a treatment for this type of AAU. HLA-B27-positive monocytes isolated from human peripheral blood were stimulated with Vibrio cholera lipopolysaccharide (LPS) for 12 hours.

2012-05-31 | E-GEOD-37588 | biostudies-arrayexpress

New insights into key genes and pathways involved in the pathogenesis of HLA-B27-associated acute anterior uveitis

2012-06-01 | GSE37588 | GEO

Degradation of misfolded HLA B*2704 (associated with disease) involves UPR, autophagy and aggresomes whereas degradation of HLA B*2709 (non-associated with disease) involves the endosomal-lysosomal pathway

Project description:Ankylosing spondylitis (AS) belongs to a group of diseases, called spondyloarthropathies (SpA), which are strongly associated with the genetic marker, HLA-B27. AS is characterized by inflammation of joints, and primarily affects the spine. Over 200 subtypes of HLA B27 are known, owing to high polymorphism. Some are strongly associated with disease (e.g., B*2704) whereas others are rarely associated (e.g., B*2709). Misfolding of HLA-B27 molecules [as dimers, or as high molecular weight (HMW) oligomers] is one of several hypotheses proposed. Our group has previously established the existence of HMW species of HLA-B27 in AS patients. Still, very little is known about the mechanisms underlying differences in pathogenic outcomes of different HLA-B27 subtypes. We conducted a proteomics-based evaluation of the differential disease association of HLA B*2704 and B*2709, using stable transfectants of genes encoding the two proteins.

2021-12-23 | PXD027999 | Pride

HLA B-27 rats peptidome - The HLA-B27 peptidome in vivo in spondyloarthritis-susceptible HLA-B27 transgenic rats and the effect of ERAP1 deletion

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2017-02-13 | PXD005502 | Pride

Homo sapiens

Project description:B27 modulation of LPS response

| PRJNA94421 | ENA

STAT1 deficiency underlies a proinflammatory imprint of naive CD4+ T cells in spondyloarthritis [ChIP-Seq]

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2014-01-17 | E-MEXP-3808 | biostudies-arrayexpress

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2023-04-15 | PXD024989 | Pride

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