A role for oncostatin M in inflammatory bowel disease

Kim, Walter M.; Kaser, Arthur; Blumberg, Richard S.

doi:10.1038/nm.4338

Cited by 24 publications

(19 citation statements)

References 13 publications

(14 reference statements)

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“…These predictions agreed with previous studies implicating IL1A and IL1B, TNF, IFNG, NFκB, CSF2, and TGFB in pediatric IBD [26,27]. Also, OSM has been implicated in adult IBD patients [28][29][30]. It is important to note that the upstream regulators were predicted based on their known effects on downstream groups of genes.…”

Section: Identification Of Pathways and Upstream Regulators Insupporting

confidence: 88%

Meta-Analysis of Expression Profiling Data Indicates Need for Combinatorial Biomarkers in Pediatric Ulcerative Colitis

Lee

Gawel

et al. 2020

Journal of Immunology Research

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Background. Unbiased studies using different genome-wide methods have identified a great number of candidate biomarkers for diagnosis and treatment response in pediatric ulcerative colitis (UC). However, clinical translation has been proven difficult. Here, we hypothesized that one reason could be differences between inflammatory responses in an inflamed gut and in peripheral blood cells. Methods. We performed meta-analysis of gene expression microarray data from intestinal biopsies and whole blood cells (WBC) from pediatric patients with UC and healthy controls in order to identify overlapping pathways, predicted upstream regulators, and potential biomarkers. Results. Analyses of profiling datasets from colonic biopsies showed good agreement between different studies regarding pathways and predicted upstream regulators. The most activated predicted upstream regulators included TNF, which is known to have a key pathogenic and therapeutic role in pediatric UC. Despite this, the expression levels of TNF were increased in neither colonic biopsies nor WBC. A potential explanation was increased expression of TNFR2, one of the membrane-bound receptors of TNF in the inflamed colon. Further analyses showed a similar pattern of complex relations between the expression levels of the regulators and their receptors. We also found limited overlap between pathways and predicted upstream regulators in colonic biopsies and WBC. An extended search including all differentially expressed genes that overlapped between colonic biopsies and WBC only resulted in identification of three potential biomarkers involved in the regulation of intestinal inflammation. However, two had been previously proposed in adult inflammatory bowel diseases (IBD), namely, MMP9 and PROK2. Conclusions. Our findings indicate that biomarker identification in pediatric UC is complicated by the involvement of multiple pathways, each of which includes many different types of genes in the blood or inflamed intestine. Therefore, further studies for identification of combinatorial biomarkers are warranted. Our study may provide candidate biomarkers for such studies.

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Section: Identification Of Pathways and Upstream Regulators Insupporting

confidence: 88%

Meta-Analysis of Expression Profiling Data Indicates Need for Combinatorial Biomarkers in Pediatric Ulcerative Colitis

Lee

Gawel

et al. 2020

Journal of Immunology Research

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“…As OSM has been suggested to have a progressive effect in chronic inflammatory diseases such as, RA[54] and inflammatory bowel disease[36,55], it has been proposed as a possible pharmaceutical target to suppress inflammation in these diseases[36,54,55] and the effect of anti-OSM treatment in RA has already been investigated in a phase 2 clinical trial[54]. However, considering the anti-atherogenic effects and positive effect of OSM on survival in the present study, we strongly recommend that cardiovascular disease markers and survival are carefully monitored when testing an OSM inhibiting approach.…”

Section: Discussionmentioning

confidence: 99%

Oncostatin M reduces atherosclerosis development in APOE*3Leiden.CETP mice and is associated with increased survival probability in humans

et al. 2019

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Objective Previous studies indicate a role for Oncostatin M (OSM) in atherosclerosis and other chronic inflammatory diseases for which inhibitory antibodies are in development. However, to date no intervention studies with OSM have been performed, and its relation to coronary heart disease (CHD) has not been studied. Approach and results Gene expression analysis on human normal arteries (n = 10) and late stage/advanced carotid atherosclerotic arteries (n = 127) and in situ hybridization on early human plaques (n = 9) showed that OSM , and its receptors, OSM receptor ( OSMR ) and Leukemia Inhibitory Factor Receptor ( LIFR ) are expressed in normal arteries and atherosclerotic plaques. Chronic OSM administration in APOE*3Leiden.CETP mice (n = 15/group) increased plasma E-selectin levels and monocyte adhesion to the activated endothelium independently of cholesterol but reduced the amount of inflammatory Ly-6C High monocytes and atherosclerotic lesion size and severity. Using aptamer-based proteomics profiling assays high circulating OSM levels were shown to correlate with post incident CHD survival probability in the AGES‐Reykjavik study (n = 5457). Conclusions Chronic OSM administration in APOE*3Leiden.CETP mice reduced atherosclerosis development. In line, higher serum OSM levels were correlated with improved post incident CHD survival probability in patients, suggesting a protective cardiovascular effect.

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“…A recent interesting study showed the cytokine oncostatin M (OSM) to be highly upregulated in inflamed mucosal tissue of IBD patients [ 115 ]. The OSM receptor (OSMR) is expressed by nonhematopoietic and nonepithelial intestinal stromal cells, which respond to OSM by producing various pro-inflammatory molecules, including IL-6, the leukocyte adhesion factor ICAM1, and chemokines that attract neutrophils, monocytes, and T-cells [ 116 ]. However, in a counter regulatory mechanism, OSM promotes epithelial repair during inflammation [ 117 ].…”

Section: Cytokine Regulation In Intestinal Pathologymentioning

confidence: 99%

Cytokine-Mediated Crosstalk between Immune Cells and Epithelial Cells in the Gut

Mahapatro

Erkert

Becker

2021

Cells

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Cytokines are small proteins that are secreted by a vast majority of cell types in the gut. They not only establish cell-to-cell interactions and facilitate cellular signaling, but also regulate both innate and adaptive immune responses, thereby playing a central role in genetic, inflammatory, and infectious diseases of the gut. Both, immune cells and gut epithelial cells, play important roles in intestinal disease development. The epithelium is located in between the mucosal immune system and the gut microbiome. It not only establishes an efficient barrier against gut microbes, but it also signals information from the gut lumen and its composition to the immune cell compartment. Communication across the epithelial cell layer also occurs in the other direction. Intestinal epithelial cells respond to immune cell cytokines and their response influences and shapes the microbial community within the gut lumen. Thus, the epithelium should be seen as a translator or a moderator between the microbiota and the mucosal immune system. Proper communication across the epithelium seems to be a key to gut homeostasis. Indeed, current genome-wide association studies for intestinal disorders have identified several disease susceptibility loci, which map cytokine signatures and their related signaling genes. A thorough understanding of this tightly regulated cytokine signaling network is crucial. The main objective of this review was to shed light on how cytokines can orchestrate epithelial functions such as proliferation, cell death, permeability, microbe interaction, and barrier maintenance, thereby safeguarding host health. In addition, cytokine-mediated therapy for inflammation and cancer are discussed.

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A role for oncostatin M in inflammatory bowel disease

Abstract: A new study identifies oncostatin M (OSM) as a potential biomarker and therapeutic target for anti-tumor necrosis factor (TNF)-refractory inflammatory bowel disease (IBD), and pinpoints mucosal stromal cells as key players in OSM-mediated inflammation.

Cited by 24 publications

References 13 publications

Meta-Analysis of Expression Profiling Data Indicates Need for Combinatorial Biomarkers in Pediatric Ulcerative Colitis

Meta-Analysis of Expression Profiling Data Indicates Need for Combinatorial Biomarkers in Pediatric Ulcerative Colitis

Oncostatin M reduces atherosclerosis development in APOE*3Leiden.CETP mice and is associated with increased survival probability in humans

Cytokine-Mediated Crosstalk between Immune Cells and Epithelial Cells in the Gut

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