RESUMEN
Con A hepatitis is regarded as a T cell-mediated model of acute liver injury. Mincle is a C-type lectin receptor that is critical in the immune response to mycobacteria and fungi but does not have a well-defined role in preclinical models of non-pathogen-mediated inflammation. Because Mincle can ligate the cell death ligand SAP130, we postulated that Mincle signaling drives intrahepatic inflammation and liver injury in Con A hepatitis. Acute liver injury was assessed in the murine Con A hepatitis model using C57BL/6, Mincle(-/-), and Dectin-1(-/-) mice. The role of C/EBPß and hypoxia-inducible factor-1α (HIF-1α) signaling was assessed using selective inhibitors. We found that Mincle was highly expressed in hepatic innate inflammatory cells and endothelial cells in both mice and humans. Furthermore, sterile Mincle ligands and Mincle signaling intermediates were increased in the murine liver in Con A hepatitis. Most significantly, Mincle deletion or blockade protected against Con A hepatitis, whereas Mincle ligation exacerbated disease. Bone marrow chimeric and adoptive transfer experiments suggested that Mincle signaling in infiltrating myeloid cells dictates disease phenotype. Conversely, signaling via other C-type lectin receptors did not alter disease course. Mechanistically, we found that Mincle blockade decreased the NF-κß-related signaling intermediates C/EBPß and HIF-1α, both of which are necessary in macrophage-mediated inflammatory responses. Accordingly, Mincle deletion lowered production of nitrites in Con A hepatitis and inhibition of both C/EBPß and HIF-1α reduced the severity of liver disease. Our work implicates a novel innate immune driver of Con A hepatitis and, more broadly, suggests a potential role for Mincle in diseases governed by sterile inflammation.
Asunto(s)
Concanavalina A/inmunología , Hepatitis/inmunología , Lectinas Tipo C/inmunología , Proteínas de la Membrana/inmunología , Transducción de Señal/inmunología , Animales , Modelos Animales de Enfermedad , Hepatitis/metabolismo , Humanos , Inflamación/inmunología , Lectinas Tipo C/deficiencia , Leucocitos Mononucleares , Masculino , Proteínas de la Membrana/deficiencia , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Noqueados , Nitritos/metabolismoRESUMEN
[This corrects the article DOI: 10.1055/s-0039-1700497.].
RESUMEN
Background Hemorrhoids are vascular structures in the anal canal which are seldom used to evaluate vascular diseases. Cigarette smoking is well-known to cause both arterial and venous vascular injuries. However, the impact of smoking on hemorrhoid vasculature is unknown. Objective Considering that vasculature in the hemorrhoids has the same anatomy and pathophysiology of vascular damage as other systemic vasculatures, we conducted this study to evaluate the relation between smoking and incidence of hemorrhoidal vascular injury. Design and Data Analysis Retrospective review of all the screening colonoscopies performed at our Department of Gastroenterology (predominantly serving urban minority population) over 3 years was conducted and patients with recorded smoking history were included in the study ( n = 242). Fisher's exact test with two-tailed p -value and odds ratio were used to evaluate for the association between smoking and incidence of hemorrhoids. Results We studied 242 subjects and found statistically significant association between smoking and hemorrhoids ( p < 0.05) with the risk of developing hemorrhoids among smokers being 2.4 times that of a nonsmoker. We further noted no significant difference in the incidence of hemorrhoidal vascular injuries between the past versus current smokers and male versus female smokers. Conclusion This is one of the first studies to establish an association between smoking and hemorrhoids. Our study shows that the hemorrhoidal vasculature is impacted by smoking similar to other vascular systems. This study sheds light on the possibility of evaluating hemorrhoids for clues of other systemic and gastrointestinal vascular damage. This correlation can add clinical value especially given the flexibility of assessing hemorrhoids as an outpatient in a cost effective and comfortable manner.
RESUMEN
Granular cell tumors are predominantly benign, occurring more commonly in women, with about 10% developing in the gastrointestinal tract. Rectal location of this tumor is very rare. We herein report one such case of a 61-year-old man with granular cell tumor in the rectum who underwent endoscopic curative resection.