TRPV1 and TRPA1 in cutaneous neurogenic and chronic inflammation: pro-inflammatory response induced by their activation and their sensitization

Cutaneous neurogenic inflammation (CNI) is inflammation that is induced (or enhanced) in the skin by the release of neuropeptides from sensory nerve endings. Clinical manifestations are mainly sensory and vascular disorders such as pruritus and erythema. Transient receptor potential vanilloid 1 and ankyrin 1 (TRPV1 and TRPA1, respectively) are non-selective cation channels known to specifically participate in pain and CNI. Both TRPV1 and TRPA1 are co-expressed in a large subset of sensory nerves, where they integrate numerous noxious stimuli. It is now clear that the expression of both channels also extends far beyond the sensory nerves in the skin, occuring also in keratinocytes, mast cells, dendritic cells, and endothelial cells. In these non-neuronal cells, TRPV1 and TRPA1 also act as nociceptive sensors and potentiate the inflammatory process. This review discusses the role of TRPV1 and TRPA1 in the modulation of inflammatory genes that leads to or maintains CNI in sensory neurons and non-neuronal skin cells. In addition, this review provides a summary of current research on the intracellular sensitization pathways of both TRP channels by other endogenous inflammatory mediators that promote the self-maintenance of CNI.

Increasing of HER2 membranar density in human glioblastoma U251MG cell line established in a new nude mice model.

Glioblastoma multiform (GBM) remains the most devastating primary tumour in neuro-oncology. Human Epithelial Receptor Type 2 (HER2) is a transmembrane tyrosine/kinase receptor that is important for cancer growth. HER2 is not expressed in adult glial cells, but its expression increases with the degree of astrocytomas anaplasia. We have recently demonstrated the ability of anti-HER2 antibodies to induce in vitro apoptosis GBM cell lines; this ability is correlated to HER2 density. A decreasing of tyrosine/kinase receptors density during in vitro culture was reported. No information exists about the variation of HER2 expression after in vivo implantation. For that, the two cell lines in vitro tested (U251MG, A172) were in vivo implanted. We established a U251MG in vivo model in balb/c nude mice showing an important increasing of HER2 density. The HER2 density is correlated to anti-HER2 antibody efficiency so this model will be useful for the evaluation of in vivo anti-HER2 antibody treatment.