RNA expression patterns change dramatically in human neutrophils exposed to bacteria

Subrahmanyam, Y. V. B. K.; Yamaga, Shigeru; Prashar, Yatindra; Lee, Helen H.; Hoe, Nancy P.; Kluger, Yuval; Gerstein, Mark; Goguen, Jon D.; Newburger, Peter E.; Weissman, Sherman M.

doi:10.1182/blood.v97.8.2457

Cited by 123 publications

(119 citation statements)

References 60 publications

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“…1,2,10,11,[36][37][38] Although previous studies have shown that neutrophils can undergo rapid changes in gene expression upon bacterial challenge 3,4,12,13,39 or exposure to endotoxin, 3,4,10,40 it was previously unknown if and to what extent the neutrophil alters its transcriptome as it transits from the BM through the circulation and into sites of inflammation.…”

Section: Discussionmentioning

confidence: 99%

“…It is widely recognized that neutrophils undergo apoptosiseven in the absence of any extracellular stimuli. 4,10,29,30 The Bcl-2 family, which we observed in our microarray analysis to be differentially expressed between compartments, is an important regulator of neutrophil apoptosis. 5,31 Here we found a mixed pattern with both pro-apoptosis and pro-survival genes with altered regulation, as neutrophils leave the circulation and arrive at the site of inflammation with downregulation of FasL, CR3 (Mac-1), caspase 2 and 9 and upregulation of Fas, Daxx, cIAP and NfkB.…”

Section: Death Receptor Pathwaymentioning

confidence: 99%

“…3 Subrahmanyam demonstrated that while neutrophils synthesize lower levels of protein and RNA, they are able to markedly change their gene expression following bacterial exposure. 4 The concept that neutrophils are static quiescent cells that merely kill bacteria has been replaced by the idea that neutrophils play a more active role in the host response. For example, activated neutrophils are able to secrete a variety of cytokines, 5 act as antigen-presenting cells expressing MHC Class II, 6 allow activation of T cells 7 and play an active regulatory role in angiogenesis 8 and tumoural fate.…”

Section: Introductionmentioning

confidence: 99%

“…2,10,11 Impaired clearance as well as delays in apoptotic events is critical to the progression of chronic inflammation. 3,12,13 A complex signaling interaction regulates neutrophil apoptosis and is initiated by two distinct pathways: the extrinsic pathway (death receptor pathway) and the intrinsic pathway (mitochondria pathway), where both pathways lead to activation of the characteristic caspase cascade 4,10 It is very likely that tight regulation of neutrophil apoptosis at different locations is a key feature of normal neutrophil function.…”

Section: Introductionmentioning

confidence: 99%

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Neutrophil transcriptional profile changes during transit from bone marrow to sites of inflammation

et al. 2014

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Section: Discussionmentioning

confidence: 99%

Section: Death Receptor Pathwaymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Neutrophil transcriptional profile changes during transit from bone marrow to sites of inflammation

et al. 2014

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“…Peptides derived from pgrn, the granulin/ epithelins (grn/epi), were isolated from neutrophils (2), and GRN is transiently upregulated in neutrophils exposed to Escherichia coli K12 (55). Microarray studies show that GRN is expressed in CD34 ϩ bone marrow cells (20) and is upregulated in acute myeloid leukemia blasts vs. normal progenitor CD34 ϩ cells (62).…”

mentioning

confidence: 99%

Regulation of progranulin expression in myeloid cells

Ong

He²,

Kriazhev³

et al. 2006

American Journal of Physiology-Regulatory, Integrative and Comp

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Progranulin (pgrn; granulin-epithelin precursor, PC-cell-derived growth factor, or acrogranin) is a multifunctional secreted glycoprotein implicated in tumorigenesis, development, inflammation, and repair. It is highly expressed in macrophage and monocyte-derived dendritic cells. Here we investigate its regulation in myeloid cells. All-trans retinoic acid (ATRA) increased pgrn mRNA levels in myelomonocytic cells (CD34 ϩ progenitors; monoblastic U-937; monocytic THP-1; progranulocytic HL-60; macrophage RAW 264.7) but not in nonmyeloid cells tested. Interleukin-4 impaired basal expression of pgrn in U-937. Differentiation agents DMSO, and, in U-937 only, phorbol ester [phorbol 12-myristate,13-acetate (PMA)] elevated pgrn mRNA expression late in differentiation, suggestive of roles for pgrn in more mature terminally differentiated granulocyte/monocytes rather than during growth or differentiation. The response of pgrn mRNA to ATRA differs in U-937 and HL-60 lineages. In U-937, ATRA and chemical differentiation agents greatly increased pgrn mRNA stability, whereas, in HL-60, ATRA accelerated pgrn mRNA turnover. The initial upregulation of pgrn mRNA after stimulation with ATRA was independent of de novo protein synthesis in U-937 but not HL-60. Chemical blockade of nuclear factor-B (NF-B) activation impaired ATRAstimulated pgrn expression in HL-60 but not U-937, whereas in U-937 it blocked PMA-induced pgrn mRNA expression, suggestive of cellspecific roles for NF-B in determining pgrn mRNA levels. We propose that: 1) ATRA regulates pgrn mRNA levels in myelomonocytic cells; 2) ATRA acts in a cell-specific manner involving the differential control of mRNA stability and differential requirement for NF-B signaling; and 3) elevated pgrn mRNA expression is characteristic of more mature cells and does not stimulate differentiation.granulin; stem cell factor; colony-stimulating factor THE GRANULIN-EPITHELIN precursor progranulin (pgrn; see Ref. 4), which is also called proepithelin (47), PC-cell-derived growth factor (66), or acrogranin (1), is a multifunctional regulatory protein that promotes mitosis, survival, and migration in many cell types (43). It stimulates growth factor-related signaling pathways such as the phosphorylation of shc, p44/42 mitogen-activated protein kinase, phosphatidylinositol 3-kinase, protein kinase B/AKT, and the p70 S6 kinase (24,35,65) and contributes to carcinogenesis in breast (51), ovarian (16,26), renal (18), hepatocellular (10), and prostate (44) cancers, gliomas (33), and multiple myelomas (63). Physiologically, pgrn is involved in wound repair (25,67) and is expressed during development (8) where it regulates cavitation in preimplantation embryos (17), blastocyst hatching (48), and malespecific differentiation of the neonatal hypothalamus (56,58).The granulin (GRN) gene is highly expressed in monocytederived cells, being the 17th and 30th most abundant transcript in human macrophage (9) and monocyte-derived dendritic cells (21), respectively. Peptides derived from pgrn, the granulin/ epit...

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Racial differences in gene‐specific DNA methylation levels are present at birth

Adkins

Krushkal

Tylavsky

et al. 2011

Birth Defects Research

143

131

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BACKGROUND DNA methylation patterns differ among children and adults and play an unambiguous role in several disease processes, particularly cancers. The origin of these differences are inadequately understood, and this is a question of specific relevance to childhood and adult cancer. METHODS DNA methylation levels at 26,485 autosomal CpGs were assayed in 201 newborns (107 African-American and 94 Caucasian). Nonparametric analyses were performed to examine the relation between these methylation levels and maternal parity, maternal age, newborn gestational age, newborn gender,and newborn race. To identify the possible influences of confounding, stratification was additionally performed by a second and third variable. For genes containing CpGs with significant differences in DNA methylation levels between races, analyses were performed to identify highly represented gene ontological terms and functional pathways. RESULTS 13.7% (3,623) of the autosomal CpGs exhibited significantly different levels of DNA methylation between African-Americans and Caucasians. 2% of autosomal CpGs had significantly different DNA methylation levels between male and female newborns. Cancer pathways, including four (pancreatic, prostate, bladder, and melanoma) with substantial differences in incidence between the races, were highly represented among the genes containing significant race-divergent CpGs. CONCLUSIONS At birth, there are significantly different DNA methylation levels between African-Americans and Caucasians at a subset of CpG dinucleotides. It is possible that some of the epigenetic precursors to cancer exist at birth and that these differences partially explain the different incidence rates of specific cancers between the races.

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RNA expression patterns change dramatically in human neutrophils exposed to bacteria

Cited by 123 publications

References 60 publications

Neutrophil transcriptional profile changes during transit from bone marrow to sites of inflammation

Neutrophil transcriptional profile changes during transit from bone marrow to sites of inflammation

Regulation of progranulin expression in myeloid cells

Racial differences in gene‐specific DNA methylation levels are present at birth

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