Inflammation is a host response to tissue damage that leads to the production of cytokines that activate stromal cells including vascular endothelial cells. Activation of the latter enables the recruitment of white blood cells from the circulating blood to the damaged tissue. White blood cells help to clear the area of damaged tissue and microorganisms and start tissue repair. There is great interest in understanding these mechanisms because they can form the basis for development of new drugs useful to treat disorders of chronic inflammation such as rheumatoid arthritis, inflammatory disease, psoriasis and others. The aim of our research is to explore how the cytokine IL-33 and the Notch signalling system can be targeted to modulate inflammation and fibrosis.

• We have discovered that inhibition of endothelial Notch signalling attenuates inflammation and we now show that selective inhibition of two Notch receptors inhibits murine arthritis. We are now generating recombinant human antibodies to these receptors with a selective ligand-neutralizing profile that will be subject to preclinical trials.
• We have generated IL-33-deficient rats by means of CRISPR/Cas9 technology, mice a completely different regulation and expression pattern when compared man and most other mammals including the rat. We reveal interesting responses in a model of endotoxemian designed to resemble sepsis.
• We have discovered that IL-33 modulates the differentiation of fibroblast during experimental kidney fibrosis.
• We have discovered that IL-33 is induced by hypoosmosis in human keratinocytes, viewing this as an epidermal homeostatic response.

Contact information:

Professor Guttorm Haraldsen Department of Pathology Oslo University Hospital Rikshospitalet PO Box 4950 Nydalen NO-0424 Oslo, Norway, Tel: +47 92401962
E-mail: gharalds@rr-research.no 

Contact information:

Professor Guttorm Haraldsen Department of Pathology Oslo University Hospital Rikshospitalet PO Box 4950 Nydalen NO-0424 Oslo, Norway, Tel: +47 92401962
E-mail: gharalds@rr-research.no