Specific Inflammatory Stimuli Lead to Distinct Platelet Responses in Mice and Humans

Beaulieu, Lea M.; Clancy, Lauren; Tanrıverdi, Kahraman; Benjamin, Emelia J.; Kramer, Carolyn D.; Weinberg, Ellen O.; He, Xianbao; Mekasha, Samrawit; Mick, Eric; Ingalls, Robin R.; Genco, Caroline A.; Freedman, Jane E.

doi:10.1371/journal.pone.0131688

Cited by 8 publications

(6 citation statements)

References 50 publications

(88 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…SNORA53, another small nucleolar RNA involved in rRNA processing, has not been previously explored. The theme of inflammatory and RNA related transcripts being affected by diet was also seen previously in ApoE-/-mice fed a high-fat diet (49).…”

Section: Discussionsupporting

confidence: 74%

Platelet functional and transcriptional changes induced by intralipid infusion

Beaulieu¹,

Vitseva²,

Tanrıverdi³

et al. 2016

Thromb Haemost

Self Cite

View full text Add to dashboard Cite

Multiple studies have shown the effects of long-term exposure to high-fat or western diets on the vascular system. There is limited knowledge on the acute effects of high circulating fat levels, specifically on platelets, which have a role in many processes, including thrombosis and inflammation. This study investigated the effects of acute, high-fat exposure on platelet function and transcript profile. Twenty healthy participants were given an intravenous infusion of 20% Intralipid emulsion and heparin over 6 hours. Blood samples were taken prior to and the day after infusion to measure platelet function and transcript expression levels. Platelet aggregation was not significantly affected by Intralipid infusion, but, when mitochondria function was inhibited by carbonyl cyanide 3-chlorophenylhydrazone (CCCP) or oligomycin, platelet aggregation was higher in the post-infusion state compared to baseline. Through RNA sequencing, and verified by RT-qPCR, 902 miRNAs and 617 mRNAs were affected by Intralipid infusion. MicroRNAs increased include miR-4259 and miR-346, while miR-517b and miR-517c are both decreased. Pathway analysis identified two clusters significantly enriched, including cell motility. In conclusion, acute exposure to high fat affects mitochondrial-dependent platelet function, as well as the transcript profile.

show abstract

Section: Discussionsupporting

confidence: 74%

Platelet functional and transcriptional changes induced by intralipid infusion

Beaulieu¹,

Vitseva²,

Tanrıverdi³

et al. 2016

Thromb Haemost

Self Cite

View full text Add to dashboard Cite

show abstract

“…RPL21 is upregulated in murine platelet cells following Chlamydia pneumoniae infection, implicating it in immune response to bacterial infection. In addition, C. pneumoniae has been shown to stimulate the TLR2 immune response by innate immune cells [38].…”

Section: Discussionmentioning

confidence: 99%

Prebiotic Galactooligosaccharide Supplementation in Adults with Ulcerative Colitis: Exploring the Impact on Peripheral Blood Gene Expression, Gut Microbiota, and Clinical Symptoms

et al. 2021

View full text Add to dashboard Cite

Prebiotics may promote immune homeostasis and reduce sub-clinical inflammation in humans. This study investigated the effect of prebiotic galactooligosaccharide (GOS) supplementation in colonic inflammation. Seventeen patients with active ulcerative colitis (UC) consumed 2.8 g/d GOS for 6 weeks. At baseline and 6 weeks, gene expression (microarray), fecal calprotectin (ELISA), microbiota (16S rRNA), short-chain fatty acids (SCFAs; gas-liquid chromatography), and clinical outcomes (simple clinical colitis activity index (SCCAI), gastrointestinal symptom rating scale (GSRS), and Bristol stool form scale (BSFS)) were measured. Following prebiotics, clinical scores (SCCAI), fecal calprotectin, SCFAs, and pH were unchanged. Five genes were upregulated and two downregulated. Normal stool proportion (BSFS) increased (49% vs. 70%, p = 0.024), and the incidence (46% vs. 23%, p = 0.016) and severity (0.7 vs. 0.5, p = 0.048) of loose stool (GSRS), along with urgency (SCCAI) scores (1.0 vs. 0.5, p = 0.011), were reduced. In patients with a baseline SCCAI ≤2, prebiotics increased the relative abundance of Bifidobacterium from 1.65% (1.97) to 3.99% (5.37) (p = 0.046) and Christensenellaceae from 0.13% (0.33) to 0.31% (0.76) (p = 0.043). Prebiotics did not lower clinical scores or inflammation but normalized stools. Bifidobacterium and Christensenellaceae proportions only increased in patients with less active diseases, indicating that the prebiotic effect may depend on disease activity. A controlled study is required to validate these observations.

show abstract

“…RNA m 6 A methylation regulates RNA splicing, translocation, stability, and translation into protein (3)(4)(5)(6). These genes with changed m 6 A peaks identified in C. parvum-infected cells cover a broad range of gene categories among the most enriched pathways in both the newly gained and lost m 6 A methylation, including immune-related genes, genes for RNA splicing and translation, mitochondrion functions, and cell proliferation (57)(58)(59)(60)(61). Activation of innate epithelial defense and dysfunction of mitochondrion and cell proliferation have previously demonstrated in intestinal epithelial cells following C. parvum infection (62,63).…”

Section: Discussionmentioning

confidence: 99%

m6A mRNA Methylation Regulates Epithelial Innate Antimicrobial Defense Against Cryptosporidial Infection

Xia

et al. 2021

Front. Immunol.

View full text Add to dashboard Cite

Increasing evidence supports that N6-methyladenosine (m6A) mRNA modification may play an important role in regulating immune responses. Intestinal epithelial cells orchestrate gastrointestinal mucosal innate defense to microbial infection, but underlying mechanisms are still not fully understood. In this study, we present data demonstrating significant alterations in the topology of host m6A mRNA methylome in intestinal epithelial cells following infection by Cryptosporidium parvum, a coccidian parasite that infects the gastrointestinal epithelium and causes a self-limited disease in immunocompetent individuals but a life-threatening diarrheal disease in AIDS patients. Altered m6A methylation in mRNAs in intestinal epithelial cells following C. parvum infection is associated with downregulation of alpha-ketoglutarate-dependent dioxygenase alkB homolog 5 and the fat mass and obesity-associated protein with the involvement of NF-кB signaling. Functionally, m6A methylation statuses influence intestinal epithelial innate defense against C. parvum infection. Specifically, expression levels of immune-related genes, such as the immunity-related GTPase family M member 2 and interferon gamma induced GTPase, are increased in infected cells with a decreased m6A mRNA methylation. Our data support that intestinal epithelial cells display significant alterations in the topology of their m6A mRNA methylome in response to C. parvum infection with the involvement of activation of the NF-кB signaling pathway, a process that modulates expression of specific immune-related genes and contributes to fine regulation of epithelial antimicrobial defense.

show abstract

Specific Inflammatory Stimuli Lead to Distinct Platelet Responses in Mice and Humans

Cited by 8 publications

References 50 publications

Platelet functional and transcriptional changes induced by intralipid infusion

Platelet functional and transcriptional changes induced by intralipid infusion

Prebiotic Galactooligosaccharide Supplementation in Adults with Ulcerative Colitis: Exploring the Impact on Peripheral Blood Gene Expression, Gut Microbiota, and Clinical Symptoms

m6A mRNA Methylation Regulates Epithelial Innate Antimicrobial Defense Against Cryptosporidial Infection

Contact Info

Product

Resources

About