Johannes Schwenck
Eberhard Karls University, Germany
Title: NF-ï«B and reactive oxygen species (ROS) differentially regulate acute and chronic delayed type hypersensitivity reactions (DTHR)
Biography
Biography: Johannes Schwenck
Abstract
NF-ï«B and ROS are crucial regulators of inflammation with considerable crosstalk between each other. Using non invasive in vivo optical imaging (OI) we uncovered the dynamics of ROS and NF-ï«B-activation in a model of acute and chronic DTHR. We assessed NF-ï«B-activation in NF-ï«B luciferase reporter mice (n=10) and ROS expression with a ROS detecting chemiluminescence probe (L-012, n=8) using in vivo OI. Mice were sensitized with TNCB at the abdomen and challenged at the right ear 7 days later (acute DTHR). To induce chronic DTHR we challenged mice every 48 hours up to 5 times. Ear-thickness (ET) and in vivo optical imaging (OI) was measured 0-24 hours after the 1st, 3rd and 5th challenge. We analysed ear tissue by histology and RT-PCR. In acute CHSR ET increased steadily until 24 hours, whereas ROS and NF-ï«B activity was first detectable 12 hours after the 1st challenge and peaked at 24 hour. After the 3rd challenge we measured at 4 hours enhanced ROS and NF-ï«B activity, which culminated at 12 hours. After the 5th challenge ROS peaked at 4 hours, whereas NF-ï«B activity increased till 12 hours. Histology revealed a strong edema in acute CHSR and massive tissue remodelling and a dense leukocyte infiltrate during chronic CHSR. ROS induced HO-1-mRNA was enhanced after the 1st and 3rd challenge. NF-ï«B driven IL-1β and IL-6-mRNA was impressively elevated after the 3rd, but not after the 1st and 5th challenge. In vivo OI uncovered the differential temporal dynamics of ROS and NF-ï«B expression during acute and chronic CHSR. This opens new windows of opportunity for innovative treatments of DTHR like rheumatoid arthritis.