14 research outputs found
Participation of corticotropin releasing hormone (CRH) in the inflammatory process
The term Inflammatory bowel disease (IBD) refers to a chronic inflammatory,
relapsing disease represented mainly by ulcerative colitis (U.C.) and Crohn's disease
(C.D.). The aetiology of IBD has not yet been elucidated, a fact that contributes to
lack of specific effective treatments. The prevailing recent studies, support the role of
disruption of the balance of intestinal barrier, which is determined by the interaction
between genetic background and the environment. The result of this disorder is the
dysfunction of the immune system, mainly the innate immune responses, and the
development of chronic active inflammation. In previous studies the proinflammatory
effects of corticotrophin releasing hormone / factor (CRH/CRF), a neuropeptide
acting as the major mediator of the stress response, in the human and rodent
gastrointestinal system have been demonstrated. By means of an experimental model
that resembles ulcerative colitis and is linked with innate immunity, the relation
between the lack of CRH and the increased susceptibility to disease development was
demonstrated. Aiming to investigate the role of CRH in experimental IBD, the course
of DSS colitis during the termination of inflammatory response and the repair of
tissue injury was observed. Surprisingly, the disease progressed in Crh-/- mice,
resulting to their severely compromised survival 5 days after cessation of DSS
treatment, while all Crh+/+ mice recovered as expected. This development was
characterized by significant continuous body weight loss, active inflammation with
evidence of increased angiogenesis, dysfunctional regeneration of the inflamed
epithelium and development of fibrosis. This picture was not reversed after
normalization of glulcocorticoid levels of the Crh-/- mice, in further support of the
hypothesis of direct CRH action in the development of ulcerative colitis. In
conclusion, these findings demonstrate the requirement of CRH for the epithelial
repair to occur following colitis induction, and the development of adaptive responses
in colitis and the resolution of inflammation
How to apply the life cycle thinking in the construction sector at local policy level: a survey from the European F.R.E.S.H. project
In the context of the European F.R.E.S.H. project (Interreg IVC Programme), this paper presents the results of the survey on Eco-design planning tools, i.e. any tool which can be used to plan or develop an eco-design strategy using the life cycle thinking at local policy level, with regard to the construction sector. A questionnaire was distributed to the eight partner regions involved in the project and six good practices, referring to different aspect of the construction supply chain, emerged to be relevant. For every good practice at least three aspects to be transferred have been identified and discussed, with regard to both technical matters and policy level. Through this in-depth analysis we concluded that what can help local authorities in the definition of their innovation strategy is spreading the adoption of tools, both at regulatory and management level, that help in the assessment of all the aspects of sustainable construction supply chain
Corticotropin-Releasing factor regulates TLR4 expression in the colon and protects mice from colitis
Background & Aims Defects in the colonic innate immune response have been associated with inflammatory bowel disease (IBD). Corticotropin-releasing hormone (CRH, or corticotropin-releasing factor [CRF]) is a neuropeptide that mediates the stress response in humans, is an immunomodulatory factor with proinflammatory effects, and regulates transcription of Toll-like receptors (TLR)-2 and TLR4. We investigated the role of CRF in an innate immunitydependent mouse model of IBD. Methods Crh-/- and wild-type (Crh+/+) mice, which are glucocorticoid insufficient, were given dextran sodium sulfate in their drinking water to induce colitis; in some experiments, mice were also given glucocorticoids. Phenotypes of mice were compared; tissues were analyzed by histology and for expression of immune mediators. Results Crh-/- mice had more colonic inflammation than Crh+/+ mice, characterized by reduced numbers of crypts and severe epithelial damage and ulcerations. Colonic tissue levels of the proinflammatory factors interleukin-12 and prostaglandin E2 were increased in the Crh-/- mice. Colons of Crh -/- mice expressed lower levels of Tlr4 than wild-type mice before, but not after, colitis was induced. Administration of glucocorticoid at low levels did not prevent Crh-/- mice from developing severe colitis. Crh-/- mice were unable to recover from acute colitis, as indicated by their increased death rate. Conclusions Mice deficient in CRF down-regulate TLR4 and are more susceptible to dextran sodium sulfateinduced colitis. CRF has anti-inflammatory effects in innate immunitydependent colitis and its recovery phase; these are independent of glucocorticoid administration. CRF might therefore be developed as a therapeutic target for patients with IBD. © 2010 AGA Institute
Is ecosystem restoration worth the effort? The rehabilitation of a Finnish river affects recreational ecosystem services
Altered Toll-like Receptor 2-mediated Endotoxin Tolerance Is Related to Diminished Interferon β Production
Induction of endotoxin tolerance leads to a reduced inflammatory response after repeated challenge by LPS and is important for resolution of inflammation and prevention of tissue damage. Enterobacterial LPS is recognized by the TLR4 signaling complex, whereas LPS of some non-enterobacterial organisms is capable of signaling independently of TLR4 utilizing TLR2-mediated signal transduction instead. In this study we report that Porphyromonas gingivalis LPS, a TLR2 agonist, fails to induce a fully endotoxin tolerant state in a human monocytic cell line (THP-1) and mouse bone marrow-derived macrophages. In contrast to significantly decreased production of human IL-8 and TNF-α and, in mice, keratinocyte-derived cytokine (KC), macrophage inflammatory protein-2 (MIP-2), and TNF-α after repeated challenge with Escherichia coli LPS, cells repeatedly exposed to P. gingivalis LPS responded by producing less TNF-α but sustained elevated secretion of IL-8, KC, and MIP-2. Furthermore, in endotoxin-tolerant cells, production of IL-8 is controlled at the signaling level and correlates well with NF-κB activation, whereas TNF-α expression is blocked at the gene transcription level. Interferon β plays an important role in attenuation of chemokine expression in endotoxin-tolerized cells as shown in interferon regulatory factor-3 knock-out mice. In addition, human gingival fibroblasts, commonly known not to display LPS tolerance, were found to be tolerant to repeated challenge by LPS if pretreated with interferon β. The data suggest that the inability of the LPS-TLR2 complex to induce full endotoxin tolerance in monocytes/macrophages is related to diminished production of interferon β and may partly explain the involvement of these LPS isoforms in the pathogenesis of chronic inflammatory diseases
Altered Toll-like Receptor 2-mediated Endotoxin Tolerance Is Related to Diminished Interferon β Production
Induction of endotoxin tolerance leads to a reduced inflammatory response after repeated challenge by LPS and is important for resolution of inflammation and prevention of tissue damage. Enterobacterial LPS is recognized by the TLR4 signaling complex, whereas LPS of some non-enterobacterial organisms is capable of signaling independently of TLR4 utilizing TLR2-mediated signal transduction instead. In this study we report that Porphyromonas gingivalis LPS, a TLR2 agonist, fails to induce a fully endotoxin tolerant state in a human monocytic cell line (THP-1) and mouse bone marrow-derived macrophages. In contrast to significantly decreased production of human IL-8 and TNF-α and, in mice, keratinocyte-derived cytokine (KC), macrophage inflammatory protein-2 (MIP-2), and TNF-α after repeated challenge with Escherichia coli LPS, cells repeatedly exposed to P. gingivalis LPS responded by producing less TNF-α but sustained elevated secretion of IL-8, KC, and MIP-2. Furthermore, in endotoxin-tolerant cells, production of IL-8 is controlled at the signaling level and correlates well with NF-κB activation, whereas TNF-α expression is blocked at the gene transcription level. Interferon β plays an important role in attenuation of chemokine expression in endotoxin-tolerized cells as shown in interferon regulatory factor-3 knock-out mice. In addition, human gingival fibroblasts, commonly known not to display LPS tolerance, were found to be tolerant to repeated challenge by LPS if pretreated with interferon β. The data suggest that the inability of the LPS-TLR2 complex to induce full endotoxin tolerance in monocytes/macrophages is related to diminished production of interferon β and may partly explain the involvement of these LPS isoforms in the pathogenesis of chronic inflammatory diseases
Toll-Like Receptor 4 in Paraventricular Nucleus Mediates Visceral Hypersensitivity Induced by Maternal Separation
Corticotropin-Releasing Hormone Receptor 2 Signaling Promotes Mucosal Repair Responses after Colitis
Stress-Induced Corticotropin-Releasing Hormone-Mediated NLRP6 Inflammasome Inhibition and Transmissible Enteritis in Mice
Identification of a novel interaction between corticotropin releasing hormone (Crh) and macroautophagy
In inflammatory bowel disease (IBD), compromised restitution of the epithelial barrier contributes to disease severity. Owing to the complexity in the pathogenesis of IBD, a variety of factors have been implicated in its progress. In this study, we report a functional interaction between macroautophagy and Corticotropin Releasing Hormone (Crh) in the gut. For this purpose we used DSS colitis model on Crh ?/? or wild-type (wt) with pharmacological inhibition of autophagy. We uncovered sustained basal autophagy in the gut of Crh ?/? mice, which persisted over the course of DSS administration. Autophagy inhibition resulted in partial rescue of Crh ?/? mice, while it increased the expression of Crh in the wt gut. Similarly, Crh deficiency was associated with sustained activation of base line autophagy. In vitro models of amino acid deprivation- and LPS-induced autophagy confirmed the in vivo findings. Our results indicate a novel role for Crh in the intestinal epithelium that involves regulation of autophagy, while suggesting the complementary action of the two pathways. These data suggest the intriguing possibility that targeting Crh stimulation in the intestine may provide a novel therapeutic approach to support the integrity of the epithelial barrier and to protect from chronic colitis