Role of tyrosine-hydroxylase (TH) - positive cells during inflammatory processes in arthritis

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In rheumatoid arthritis a massive loss of tyrosine hydroxylase (TH)-positive (sympathetic) nerve fibres and a clear increase of TH-positive cells in inflamed synovial tissue of humans was found during inflammation (own previous work). Most probably these cells are sympatho-adrenergic cells (own previous work). The role these cells play in inflammation is totally unclear. Therefore, in this application, we want to scrutinise the following points: 1. Under which conditions do these cells produce catecholamines?2. How do these cells modulate the function of synovial macrophages and fibroblasts and how dothe macrophages and fibroblasts modulate the secretion of catecholamines?3. Are these cells proinflammatory and how would the their removal influence the course of experimental arthritis?4. How is TH regulated in TH-positive cells from human synovia (alternative splicing?)5. Does norepinephrine produced by these cells interfere with conversion of 17ß-estradiol to2-methoxyestradiol?These experiments will shed light on the importance of TH-positive cells in arthritis and might lead to new therapeutic principles for arthritis.