Loss of Braking Signals During Inflammation

Gilli, Francesca; Navone, Nicole Desiree; Perga, Simona; Marnetto, Fabiana; Caldano, Marzia; Capobianco, Marco; Pulizzi, Annalisa; Malucchi, Simona; Bertolotto, Antonio

doi:10.1001/archneurol.2011.32

Cited by 42 publications

(34 citation statements)

References 41 publications

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“…In contrast, expression of the SOCS2 gene [29], which acts as a negative regulator of TLR-induced DC activation, was down-regulated. Defects in negative-feedback loops regulating inflammation lead to increased inflammation-sensitive autoimmune diseases [30]. Thus, the alterations in Unc93B1 and SOCS2 may result in an enhancement of TLR activation-associated inflammation [31]–[32].…”

Section: Discussionmentioning

confidence: 99%

Alterations in Gene Array Patterns in Dendritic Cells from Aged Humans

et al. 2014

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Dendritic cells (DCs) are major antigen-presenting cells that play a key role in initiating and regulating innate and adaptive immune responses. DCs are critical mediators of tolerance and immunity. The functional properties of DCs decline with age. The purpose of this study was to define the age-associated molecular changes in DCs by gene array analysis using Affymatrix GeneChips. The expression levels of a total of 260 genes (1.8%) were significantly different (144 down-regulated and 116 upregulated) in monocyte-derived DCs (MoDCs) from aged compared to young human donors. Of the 260 differentially expressed genes, 24% were down-regulated by more than 3-fold, suggesting that a large reduction in expression occurred for a notable number of genes in the aged. Our results suggest that the genes involved in immune response to pathogens, cell migration and T cell priming display significant age-related changes. Furthermore, downregulated genes involved in cell cycle arrest and DNA replication may play a critical role in aging-associated genetic instability. These changes in gene expression provide molecular based evidence for age-associated functional abnormalities in human DCs that may be responsible for the defects in adaptive immunity observed in the elderly.

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Section: Discussionmentioning

confidence: 99%

Alterations in Gene Array Patterns in Dendritic Cells from Aged Humans

et al. 2014

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“…Downregulation of three of these genes encoding negative regulators of inflammation has been inversely correlated with relapse rate and EDSS in men and women in the initial phase of relapsing remitting MS [96]. …”

Section: Reproductive Eventsmentioning

confidence: 99%

Female Gender and Reproductive Factors Affecting Risk, Relapses and Progression in Multiple Sclerosis

D’hooghe

D’Hooghe²,

Keyser

2013

Gynecol Obstet Invest

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Multiple sclerosis (MS), a chronic inflammatory demyelina-ting and degenerative disease of the central nervous system, is a frequent cause of neurological disability in young adults. Female predominance has increased over the last decades. Although female gender carries a higher risk of developing relapsing remitting MS, being female and at child-bearing age also appears to provide some protection against cognitive decline and against progressive onset MS, an adverse predictive factor when considering long-term disability in MS. The risk of MS in women has been associated with an earlier age at menarche. In most studies, parity did not impact MS risk. However, the recently published association of higher parity and offspring number with a reduced risk of a first demyelinating event suggests a potential suppressive effect. Pregnancy in MS patients has been associated with a reduced relapse rate and a reduction of neurological symptoms, especially in the third trimester. Despite the increased relapse risk in the postpartum period, there is no indication of an adverse effect of childbirth on the long-term course of MS. Fertility treatment in MS has been associated with an increased relapse risk in the following 3-month period, especially when the procedure did not result in pregnancy and gonadotrophin-releasing hormone agonists were used. Altogether, there is substantial evidence to support a regulatory role of sex steroid hormones in MS. In the absence of correlations with single hormone blood levels, we can only speculate about the underlying mechanisms. In conclusion, the increased MS risk in women and the changes in relapse and progression risk in association with reproductive events suggest significant and complex interactions between immune, neuroendocrine and reproductive systems in MS.

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“…These results suggested that endometriosis has disparate effects on proteinase production by uterine tissue as compared to the peritoneum, which is consistent with cell-type specific actions and possibly proximal vs. distal influences of the disease milieu. The function of FAM49B has yet to be elucidated, but it has been associated with diseases that are related to immune dysregulation, such as multiple sclerosis [61]. Interestingly, immune dysfunction has also been implicated in the pathogenesis of endometriosis [16].…”

Section: Discussionmentioning

confidence: 99%

Urine, peritoneal fluid and omental fat proteomes of reproductive age women: Endometriosis-related changes and associations with endocrine disrupting chemicals

Williams

Miroshnychenko

Johansen

et al. 2015

Journal of Proteomics

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Endometriosis, ectopic growth of the uterine lining (endometrium), which affects 6–11% of reproductive age women, is associated with pelvic pain and infertility. We investigated the peritoneal fluid (PF), urine and omental fat (OF) proteomes of women with endometriosis vs. individuals with no surgically visualized endometriosis. All participants were enrolled in the NICHD-funded ENDO Study. A two-step proteomic study was performed. The first, a broad survey, employed a semi-quantitative gel LC-mass spectrometry (MS) workflow: SDS PAGE fractionation, trypsin digestion and LC–MS/MS. The results showed sample integrity but failed to detect any differences between women with and without endometriosis. The second step was a quantitative analysis of OF samples. We employed another sample set (n = 30) from women ± disease and isobaric mass-tag (iTRAQ) chemistry to label peptides and 2D LC–MS/MS for protein identification and quantification. Three proteins—matrix metalloproteinase-9, neutrophil elastase, and FAM49B—were significantly lower in abundance in samples from women with endometriosis. Interestingly, neutrophil elastase and FAM49B levels were associated with higher levels of a subset of endocrine disrupting chemicals (EDCs) that were previously measured in the same samples. The results of these experiments showed the feasibility of associating endometriosis with changes in the OF protein repertoire and EDC levels. Biological significance Endometriosis, pathological growth of the uterine lining, is associated with significant morbidities, including pain and infertility. However, the causes of this common condition are poorly understood. This study determined whether endometriosis was associated with changes in the protein composition of peritoneal fluid, urine and/or omental fat. A protein of unknown function (FAM49B) and two proteinases (metalloproteinase-9, neutrophil elastase) were down regulated in OF samples from women with versus without endometriosis. These findings suggested proteinase imbalances at sites that were distant from the endometriotic lesions. Additionally, FAM49B and neutrophil elastase levels were associated with higher levels of a subset of environmental chemicals that were quantified in the same samples, suggesting other possible associations. Thus, this work generated hypotheses that will be tested in further studies.

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Loss of Braking Signals During Inflammation

Cited by 42 publications

References 41 publications

Alterations in Gene Array Patterns in Dendritic Cells from Aged Humans

Alterations in Gene Array Patterns in Dendritic Cells from Aged Humans

Female Gender and Reproductive Factors Affecting Risk, Relapses and Progression in Multiple Sclerosis

Urine, peritoneal fluid and omental fat proteomes of reproductive age women: Endometriosis-related changes and associations with endocrine disrupting chemicals

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