Cytokine-induced gene expression at the crossroads of innate immunity, inflammation and fertility: TSG-6 and PTX3/TSG-14

Wisniewski, Hans‐Georg; Vilček, Ján

doi:10.1016/j.cytogfr.2004.01.005

Cited by 135 publications

(120 citation statements)

References 113 publications

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“…TSG-6 is a 35-kDa protein that is secreted in response to TNF-a or IL-1b and is natural modulator of inflammation. 27,28 We, and others, have shown that hMSCs suppresses excessive sterile inflammation thereby ameliorating lung injury, 5 myocardial infarction, 29 corneal injury 30 or peritonitis, 26 in part due to hMSCs activation and secretion of TSG-6. Recently, Lee et al, 7 have proposed TSG-6 mRNA levels as a biomarker to predict in vivo efficacy in suppressing inflammation of different donor-derived hMSCs prior to use.…”

Section: Discussionmentioning

confidence: 99%

Human cytomegalovirus infection of human adipose-derived stromal/stem cells restricts differentiation along the adipogenic lineage

et al. 2015

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Human adipose-derived stromal/stem cells (ASCs) display potential to be used in regenerative stem cell therapies and as treatments for inflammatory and autoimmune disorders. Despite promising use of ASCs as therapeutics, little is known about their susceptibility to infectious agents. In this study, we demonstrate that ASCs are highly susceptible to human cytomegalovirus (HCMV) infection and permissive for replication leading to release of infectious virions. Additionally, many basic ASC functions are inhibited during HCMV infection, such as differentiation and immunomodulatory potential. To our knowledge this is the first study examining potential adverse effects of HCMV infection on ASC biology. Our results suggest, that an active HCMV infection during ASC therapy may result in a poor clinical outcome due to interference by the virus.

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Section: Discussionmentioning

confidence: 99%

Human cytomegalovirus infection of human adipose-derived stromal/stem cells restricts differentiation along the adipogenic lineage

et al. 2015

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“…This expansion of the ovulatory follicle is caused by rapid HA synthesis, resulting in the formation of an HA-rich extracellular matrix. Studies in knock-out mice have shown that three genes, encoding TSG-6, pentraxin 3 (PTX3), and bikunin, one of the polypeptide chains of I␣I, are essential for the structural integrity of the cumulus cell-oocyte complex during ovulation and that the disruption of any one of these genes impairs female fertility (1,11,(52)(53)(54). It is assumed that the stability of the cumulus cell-oocyte complex matrix is achieved by crosslinking of HA.…”

Section: Discussionmentioning

confidence: 99%

“…We and others (1,(5)(6)(7)(8)(9)(10) have shown that TSG-6 protein exerts anti-inflammatory actions in murine models of acute inflammation and autoimmune arthritis. More recently, it has become clear that TSG-6 also plays an essential role in female fertility (1,11). The protein consists of two domains, the N-terminal link module and the C-terminal CUB domain.…”

Section: Tnfmentioning

confidence: 99%

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TSG-6 Protein Binding to Glycosaminoglycans

Wisniewski

Snitkin

Mindrescu

et al. 2005

Journal of Biological Chemistry

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TSG-6 protein, up-regulated in inflammatory lesions and in the ovary during ovulation, shows anti-inflammatory activity and plays an essential role in female fertility. Studies in murine models of acute inflammation and experimental arthritis demonstrated that TSG-6 has a strong anti-inflammatory and chondroprotective effect. TSG-6 protein is composed of the N-terminal link module that binds hyaluronan and a C-terminal CUB domain, present in a variety of proteins. Interactions between the isolated link module and hyaluronan have been studied extensively, but little is known about the binding of full-length TSG-6 protein to hyaluronan and other glycosaminoglycans. We show that TSG-6 protein and hyaluronan, in a temperature-dependent fashion, form a stable complex that is resistant to dissociating agents. The formation of such stable complexes may underlie the activities of TSG-6 protein in inflammation and fertility, e.g. the TSG-6-dependent cross-linking of hyaluronan in the cumulus cell-oocyte complex during ovulation. Because adhesion to hyaluronan is involved in cell trafficking in inflammatory processes, we also studied the effect of TSG-6 on cell adhesion. TSG-6 binding to immobilized hyaluronan did not interfere with subsequent adhesion of lymphoid cells. In addition to immobilized hyaluronan, full-length TSG-6 also binds free hyaluronan and all chondroitin sulfate isoforms under physiological conditions. These interactions may contribute to the localization of TSG-6 in cartilage and to its chondroprotective and anti-inflammatory effects in models of arthritis.

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“…The protein possesses potent anti-inflammatory properties, but the precise mechanism(s) is elusive and, therefore, whether its upregulation was in any way related to the aforementioned downregulation of a number of immune effector genes is unknown. 20 Thus, it is possible that certain intracellular pathogens attempt to subvert innate and acquired immune mechanisms by specifically downregulating genes critically required for generation of an effective anti-bacterial response. By contrast, certain genes contributing to the development of an immune response were upregulated.…”

Section: Transcriptional Host Response During Tularemia H Andersson Ementioning

confidence: 99%

Transcriptional profiling of the peripheral blood response during tularemia

et al. 2006

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Tularemia is a febrile disease caused by the highly contagious bacterium Francisella tularensis. We undertook an analysis of the transcriptional response in peripheral blood during the course of ulceroglandular tularemia by use of Affymetrix microarrays comprising 14 500 genes. Samples were obtained from seven individuals at five occasions during 2 weeks after the first hospital visit and convalescent samples 3 months later. In total, 265 genes were differentially expressed, 95 of which at more than one time point. The differential expression was verified with real-time quantitative polymerase chain reaction for 36 genes (R 2 ¼ 0.590). The most prominent changes were noted in samples drawn on days 2-3 and a considerable proportion of the upregulated genes appeared to represent an interferon-g-induced response and also a proapoptotic response. Genes involved in the generation of innate and acquired immune responses were found to be downregulated, presumably a pathogen-induced event. A logistic regression analysis revealed that seven genes were good predictors of the early phase of tularemia. This is the first description of the transcriptional host response to ulceroglandular tularemia and the study has identified gene subsets relevant to the pathogenesis of the disease and subsets that may serve as early diagnostic biomarkers.

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Cytokine-induced gene expression at the crossroads of innate immunity, inflammation and fertility: TSG-6 and PTX3/TSG-14

Cited by 135 publications

References 113 publications

Human cytomegalovirus infection of human adipose-derived stromal/stem cells restricts differentiation along the adipogenic lineage

Human cytomegalovirus infection of human adipose-derived stromal/stem cells restricts differentiation along the adipogenic lineage

TSG-6 Protein Binding to Glycosaminoglycans

Transcriptional profiling of the peripheral blood response during tularemia

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