Roman Mehling
Eberhard Karls University, Germany
Title: Essential role of canonical NF-B activation in T-cell driven acute and chronic contact hypersensitivity reactions (CHSR)
Biography
Biography: Roman Mehling
Abstract
Canonical NF-κB activation (p50) is involved in opposing immune functions (Cell 1995; 80:321-30). As the role of canonical NF-κB activation in adaptive immune responses is still ambiguous we analyzed acute and chronic contact hypersensitivity reactions in NF-κB-p50-/- mice. We sensitized wild-type and NF-κB-p50-/- mice at the abdomen (TNCB) and challenged one ear seven days later to elicit acute CHRS. Chronic CHSR was induced by repetitive TNCB-challenges for up to five times. CHSR was analyzed by measuring the ear thickness, histopathology and examination of ROS-stress non invasively in vivo with L-012-optical imaging (OI). In addition, we analyzed the leucocyte subsets in lymph nodes/spleens and the expression of NF-κB driven genes in inflamed ears. We determined a strongly enhanced acute and chronic CHRS in NF-κB-p50-/- mice when compared to WT mice. NF-κB-p50-/- mice exhibited an even up to two-fold increased ear thickness. H&E histology of NF-κBp50-/- mice revealed an impressively enhanced edema and a strongly pronounced leucocytic infiltrate dominated by polymorphonuclear leukocytes. Determination of ROS-stress exhibited significantly increased levels in ears from NF-κBp50-/- mice during acute and chronic CHSR. DHR-flow cytometry analysis of spleens of NF-κBp50-/- mice uncovered enhanced ROS expression by leucocytes and of CD4+CD69+ cells. Finally we uncovered an impressively enhanced IL-1β, IL-6 and TNF-alpha mRNA expression in ears of NF-κBp50-/- mice with acute and chronic CHSR. Our data suggest an anti-inflammatory role of canonical NF-κB activation in delayed-type hypersensitivity reactions. Thus, specific modulation of NF-κB signaling may be therapeutic tool for treatment of psoriasis or rheumatoid arthritis.