Μετάβαση στο κύριο περιεχόμενο

! # Ola via Alexandros G.Sfakianakis on Inoreader

Sphingosine Kinase 1 expression in peritoneal macrophages is required for colon carcinogenesis

Abstract
Accumulating evidence suggests that the sphingosine kinase 1 (SphK1)/sphingosine 1-phosphate (S1P) pathway plays a pivotal role in colon carcinogenesis. Our previous studies indicate that the SphK1/S1P pathway mediates colon carcinogenesis at least by regulating cyclooxygenase 2 (COX-2) expression and prostaglandin E2 (PGE2) production. However, the mechanisms by which this pathway regulates colon carcinogenesis are still unclear. First, we show that SphK1 deficient mice significantly attenuated azoxymethane (AOM)-induced colon carcinogenesis as measured by colon tumor incidence, multiplicity, and volume. We found that AOM activates peritoneal macrophages to induce SphK1, COX-2, and tumor necrosis factor (TNF)-α expression in WT mice. Interestingly, SphK1 knockout (KO) mice revealed significant reduction of COX-2 and TNF-α expression from AOM-activated peritoneal macrophages, suggesting that SphK1 regulates COX-2 and TNF-α expression in peritoneal macrophages. We found that inoculation of WT peritoneal macrophages restored the carcinogenic effect of AOM in Sphk1 KO mice as measured by aberrant crypt foci (ACF) formation, preneoplastic lesions of colon cancer. In addition, downregulation of SphK1 only in peritoneal macrophage by short hairpin RNA (shRNA) reduced the number of ACF per colon induced by AOM. Intraperitoneal injection of sphingolipids demonstrates that S1P enhanced AOM-induced ACF formation, while ceramide inhibited. Finally, we show that SphK inhibitor SKI-II significantly reduced the number of ACF per colon. These results suggest that SphK1 expression plays a pivotal role in the early stages of colon carcinogenesis through regulating COX-2 and TNF-α expression from activated peritoneal macrophages.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2AEhPwn
via IFTTT

Σχόλια

Δημοφιλείς αναρτήσεις από αυτό το ιστολόγιο

Does CBD Oil Lower Blood Pressure?

Does CBD Oil Lower Blood Pressure?This article was originally published at SundayScaries."
Madeline TaylorPOSTED ONJanuary 13, 2019 High blood pressure is a serious condition that currently affects thousands of adults in America. Statistics show that 33% of adults who are above the age of 20 struggle with high blood pressure and that figure reaches a whopping 66% for those in their mid-60 and over. It goes without saying that high blood pressure is becoming a nasty rising trend, which is only going to worsen if changes to the system aren't made. While there is already a substantial amount of research into hypertension, a succinct cure is yet to be found. And, thanks to the rise of natural medicines, including medical marijuana, many people now suspect that cannabis-based products could provide the answers we have been looking for with regards to lowering blood pressure in modern society.Hypertension doesn't immediately strike us as a fatal condition when you compare it to a…

Accessory Auricles: Systematic Review of Definition, Associated Conditions, and Recommendations for Clinical Practice

Abstract Accessory auricles are rare congenital abnormalities embryologically derived from the first branchial arch. Presentation may be variable with locations grouped into anatomical zones based on the frequency of location found in the literature. This study reviewed the papers between 1981 and 2017. Findings included an association with syndromes including Goldenhar, VACTERL, Treacher–Collins, Townes–Brocks, and Wolf–Hirschhorn. Based on histological and embryological evidence, the term "accessory auricle" is best used as an umbrella term to define this difference. Finally, indications are provided for imaging and laboratory investigations to guide the physician treating patients with accessory auricles. Address correspondence and reprint requests to Mark S. Lloyd, MPhil, FRCS(Plast), Department of Plastic Surgery, Autologous Ear Reconstruction Service, Birmingham Children's and Women's Hospital NHS Trust, 4th Floor, Ladywood House, Steelhouse Lane, Birmingham B4…

Efficacy and Tolerability of CyberKnife Stereotactic Robotic Radiotherapy for Primary or Secondary Orbital Lesions: A Single-Center Retrospective Experience

Technology in Cancer Research &Treatment, Volume 18, Issue , January 2019.


from A via a.sfakia on Inoreader http://bit.ly/2Qfe0Ek