Activation of the Innate immune System: The Toll-like Receptor 4 and Signalling through Ubiquitylation

2009 ◽  
pp. 451-482
Author(s):  
Bastien D. Gomperts ◽  
IJsbrand M. Kramer ◽  
Peter E.R. Tatham
2005 ◽  
Vol 193 (3) ◽  
pp. 921.e1-921.e8 ◽  
Author(s):  
Yeon Mee Kim ◽  
Roberto Romero ◽  
Seo Young Oh ◽  
Chong Jai Kim ◽  
Brian A. Kilburn ◽  
...  

Author(s):  
Amanda Almeida de Oliveira ◽  
Kenia Pedrosa Nunes

Abstract A diagnostic of hypertension increases the risk of erectile dysfunction (ED); likewise, ED can be an early sign of hypertension. In both cases, there is evidence that endothelial dysfunction is a common link between the 2 conditions. During hypertension, the sustained and widespread release of procontractile factors (e.g., angiotensin II, endothelin 1, and aldosterone) impairs the balance between vasoconstrictors and vasodilators and, in turn, detrimentally impacts vascular and erectile structures. This prohypertensive state associates with an enhancement in the generation of reactive oxygen species, which is not compensated by internal antioxidant mechanisms. Recently, the innate immune system, mainly via Toll-like receptor 4, has also been shown to actively contribute to the pathophysiology of hypertension and ED not only by inducing oxidative stress but also by sustaining a low-grade inflammatory state. Furthermore, some drugs used to treat hypertension can cause ED and, consequently, reduce compliance with the prescribed pharmacotherapy. To break down these challenges, in this review, we focus on discussing the well-established as well as the emerging mechanisms linking hypertension and ED with an emphasis on the signaling network of the vasculature and corpora cavernosa, the vascular-like structure of the penis.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 425-425
Author(s):  
Ahmet H. Elmaagacli ◽  
Michael Koldehoff ◽  
Nina K. Steckel ◽  
Heidrun Hindahl ◽  
Rudolf Trenschel ◽  
...  

Abstract The innate immune system detects invading pathogens through several pattern-recognition receptors and represents the first line of mucosal host defense. Mutations of the NOD2/CARD15 and Toll like receptor −2, −4, −9 genes have been associated with an increased incidence of inflammatory bowel disease due to a diminished response to bacterial cell wall products. Moreover, it was reported that mutations of NOD2 gene loci might be associated with an increased risk for TRM and severe GVHD in patients who underwent allogeneic blood stem cell transplantation. Here we analyzed 201 patients and their respective donors for NOD2, TLR-2, TLR-4 and TLR-9 mutations and correlated the results with the incidence of overall acute GVHD and intestinal GVHD. Further, we evaluated if the occurrence of NOD2/CARD15 and TLR allele mutations are accompanied with an increased risk for transplant-related mortality and overall survival. Mutated alleles of the NOD2 gene were observed in 17% of the patients and 16% of the donors. NOD2 gene mutations in patients and donors together were associated with an increased incidence of severe acute GVHD grade III-IV (6/11 patients; 55% versus 35/145 patients; 24%). If a mutated allele of the NOD2 gene was found either in patients or in donors only no correlation with increased incidence of severe acute GVHD was seen in this study. Patients with mutated alleles in TLR-4 genes (Asp299Gly and Thr399Ile) had a higher incidence of intestinal GVHD (p<0.02), whereas mutations of donor alleles only had no influence on the occurrence of intestinal GVHD in this analysis. No correlation with intestinal GVHD or overall acute GVHD was seen in patients with mutated alleles for TLR-2 and TLR-9. Overall survival, TRM and relapse risks was not influenced in none of the patients with mutated alleles of the innate immune system genes. Multivariate analysis including all potential factors, confirmed that that mutations of NOD2/CARD15 in patients and donors together influenced the occurrence of severe acute GVHD, whereas the occurrence of intestinal GVHD was influenced in patients by mutated alleles of TLR-4 gene. But mutations in alleles of the NOD2 or TLR-2,−4,−9 had no influence on the outcome of allogeneic transplant (TRM and overall survival) in the multivariate analysis. Since all patients in our institution had received an intestinal bacterial decontamination using metronidazole and ciprofloxacin after allogeneic stem cell transplantation, it might be speculative, if the reduction of concentrations of anaerobic bacteria in the intestinum might have protected patients from the occurrence of increased TRM. Decontamination of anaerobic bacteria is associated with a reduced risk for severe acute GVHD as reported earlier (Blood1999; 93:3267–75).


Sign in / Sign up

Export Citation Format

Share Document