Immunology
-
Glia and microglia in particular elaborate pro-inflammatory molecules that play key roles in central nervous system (CNS) disorders from neuropathic pain and epilepsy to neurodegenerative diseases. Microglia respond also to pro-inflammatory signals released from other non-neuronal cells, mainly those of immune origin such as mast cells. The latter are found in most tissues, are CNS resident, and traverse the blood-spinal cord and blood-brain barriers when barrier compromise results from CNS pathology. ⋯ N-Palmitoylethanolamine has proven efficacious in mast-cell-mediated experimental models of acute and neurogenic inflammation. This review will provide an overview of recent progress relating to the pathobiology of neuroinflammation, the role of microglia, neuroimmune interactions involving mast cells and the possibility that mast cell-microglia cross-talk contributes to the exacerbation of acute symptoms of chronic neurodegenerative disease and accelerates disease progression, as well as promoting pain transmission pathways. We will conclude by considering the therapeutic potential of treating systemic inflammation or blockade of signalling pathways from the periphery to the brain in such settings.
-
We examined the effect of interleukin-17 (IL-17) on the expression of Toll-like receptors (TLRs) in fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). We investigated the region downstream of IL-17 for TLR expression. We also investigated the downstream signals responsible for the effect of IL-17 in TLR expression. ⋯ Our results suggest that IL-17 is a major cytokine in pathogenesis on RA. The IL-17 influences the innate immune system by increasing the synovial expression of TLR2, TLR3 and TLR4. We may control TLR3 expression via the STAT3 pathway in RA FLS.