Search results for "signal transduction."
showing 10 items of 1278 documents
Blockade of interleukin 6 trans signaling suppresses T-cell resistance against apoptosis in chronic intestinal inflammation: Evidence in Crohn diseas…
2000
The pro-inflammatory cytokine interleukin (IL)-6 (refs. 1-5) can bind to cells lacking the IL-6 receptor (IL-6R) when it forms a complex with the soluble IL-6R (sIL-6R) (trans signaling). Here, we have assessed the contribution of this system to the increased resistance of mucosal T cells against apoptosis in Crohn disease (CD), a chronic inflammatory disease of the gastrointestinal tract. A neutralizing antibody against IL-6R suppressed established experimental colitis in various animal models of CD mediated by type 1 T-helper cells, by inducing apoptosis of lamina propria T cells. Similarly, specific neutralization of sIL-6R in vivo by a newly designed gp130-Fc fusion protein caused suppr…
Oxidative stress in marathon runners: interest of antioxidant supplementation
2006
We have recently reported that xanthine oxidase is involved in the generation of free radicals in exhaustive exercise. Allopurinol, an inhibitor of xanthine oxidase, prevents it. The aim of the present work was to elucidate the role of exercise-derived reactive oxygen species in the cell signalling pathways involved in the adaptation to exercise in man. We have found that exercise causes an increase in the activity of plasma xanthine oxidase and an activation of NF-κB in peripheral blood lymphocytes after marathon running. This activation is dependent on free radical formation in exercise: treatment with allopurinol completely prevents it. In animal models, we previously showed that NF-κB a…
Graves' Autoantibodies Exhibit Different Stimulating Activities in Cultures of Thyrocytes and Orbital Fibroblasts Not Reflected by Clinical Assays
2021
Background: The pathogenesis of Graves' hyperthyroidism (GH) and associated Graves' orbitopathy (GO) appears to involve stimulatory autoantibodies (thyrotropin receptor [TSHR]-stimulating antibodies [TSAbs]) that bind to and activate TSHRs on thyrocytes and orbital fibroblasts. In general, measurement of circulating TSHR antibodies by clinical assays correlates with the status of GH and GO. However, most clinical measurements of TSHR antibodies use competitive binding assays that do not distinguish between TSAbs and antibodies that bind to but do not activate TSHRs. Moreover, clinical assays for TSAbs measure stimulation of only one signaling pathway, the cyclic adenosine monophosphate (cAM…
Analysis of the gastrin-releasing peptide receptor gene in Italian patients with autism spectrum disorders
2008
The gastrin-releasing peptide receptor (GRPR) was implicated for the first time in the pathogenesis of Autism spectrum disorders (ASD) by Ishikawa-Brush et al. [Ishikawa-Brush et al. (1997): Hum Mol Genet 6: 1241-1250]. Since this original observation, only one association study [Marui et al. (2004): Brain Dev 26: 5-7] has further investigated, though unsuccessfully, the involvement of the GRPR gene in ASD. With the aim of contributing further information to this topic we have sequenced the entire coding region and the intron/exon junctions of the GRPR gene in 149 Italian autistic patients. The results of this study led to the identification of four novel point mutations, two of which, that…
Prostaglandin E2 activates the ciliary beat frequency of cultured human nasal mucosa via the second messenger cyclic adenosine monophosphate.
2001
Prostaglandins influence the ciliary beat frequency (CBF) of ciliated nasal epithelial cells and a stimulatory effect has been described for prostaglandin E2 (PGE2). Until now, it is not known whether PGE2 has direct ciliostimulatory properties or acts through a second messenger. In this study we investigated whether cyclic adenosine monophosphate (cAMP) is implicated in the signal transduction pathway of PGE2-induced activation of CBF. Ciliated cells of the nasal mucosa were cultured for up to 5 days whereafter the culture medium was removed and the cells were incubated with different concentrations of test solutions. The ciliated cells were recorded under a phase-contrast microscope and v…
Genes involved in immune response/inflammation, IGF1/insulin pathway and response to oxidative stress play a major role in the genetics of human long…
2005
In this paper, we review data of recent literature on the distribution in centenarians of candidate germ-line polymorphisms that likely affect the individual chance to reach the extreme limit of human life. On the basis of previous observations on the immunology, endocrinology and cellular biology of centenarians we focused on genes that regulate immune responses and inflammation (IL-6, IL-1 cluster, IL-10), genes involved in the insulin/IGF-I signalling pathway and genes that counteract oxidative stress (PON1). On the whole, data indicate that polymorphisms of these genes likely contribute to human longevity, in accord with observations emerging from a variety of animal models, and suggest…
Aging Negatively Affects Estrogens-Mediated Effects on Nitric Oxide Bioavailability by Shifting ERα/ERβ Balance in Female Mice
2011
AIMS: Aging is among the major causes for the lack of cardiovascular protection by estrogen (E2) during postmenopause. Our study aims to determine the mechanisms whereby aging changes E2 effects on nitric oxide (NO) production in a mouse model of accelerated senescence (SAM). METHODS AND RESULTS: Although we found no differences on NO production in females SAM prone (SAMP, aged) compared to SAM resistant (SAMR, young), by either DAF-2 fluorescence or plasmatic nitrite/nitrate (NO2/NO3), in both cases, E2 treatment increased NO production in SAMR but had no effect in SAMP. Those results are in agreement with changes of eNOS protein and gene expression. E2 up-regulated eNOS expression in SAMR…
Anti-Aging Effects of GDF11 on Skin
2020
International audience; Human skin is composed of three layers: the epidermis, the dermis, and the hypodermis. The epidermis has four major cell layers made up of keratinocytes in varying stages of progressive differentiation. Skin aging is a multi-factorial process that affects every phase of its biology and function. The expression profiles of inflammation-related genes analyzed in resident immune cells demonstrated that these cells have a strong ability to regenerate adult skin stem cells and to produce endogenous substances such as growth differentiation factor 11 (GDF11). GDF11 appears to be the key to progenitor proliferation and/or differentiation. The preservation of youthful phenot…
YAP/TAZ activity in stromal cells prevents ageing by controlling cGAS-STING
2022
Ageing is intimately connected to the induction of cell senescence(1,2), but why this is so remains poorly understood. A key challenge isthe identification of pathways that normally suppress senescence, are lost during ageing and are functionally relevant to oppose ageing(3). Here we connected the structural and functional decline of ageing tissues to attenuated function of the master effectors of cellular mechanosignalling YAP and TAZ. YAP/TAZ activity declines during physiological ageing in stromal cells, and mimicking such decline through genetic inactivation of YAP/TAZ in these cells leads to accelerated ageing. Conversely, sustaining YAP function rejuvenates old cells and opposes the e…
Tif1γ regulates the TGF-β1 receptor and promotes physiological aging of hematopoietic stem cells.
2014
The hematopoietic system declines with age. Myeloid-biased differentiation and increased incidence of myeloid malignancies feature aging of hematopoietic stem cells (HSCs), but the mechanisms involved remain uncertain. Here, we report that 4-mo-old mice deleted for transcription intermediary factor 1γ (Tif1γ) in HSCs developed an accelerated aging phenotype. To reinforce this result, we also show that Tif1γ is down-regulated in HSCs during aging in 20-mo-old wild-type mice. We established that Tif1γ controls TGF-β1 receptor (Tgfbr1) turnover. Compared with young HSCs, Tif1γ(-/-) and old HSCs are more sensitive to TGF-β signaling. Importantly, we identified two populations of HSCs specifical…