Riepl, Birgit and Graessel, Susanne and Wiest, Reiner and Fleck, Martin and Straub, Rainer H. (2010) Tumor necrosis factor and norepinephrine lower the levels of human neutrophil peptides 1-3 secretion by mixed synovial tissue cultures in osteoarthritis and rheumatoid arthritis. ARTHRITIS RESEARCH & THERAPY, 12 (3): R110. ISSN 1478-6354,
Full text not available from this repository. (Request a copy)Abstract
Introduction: Neutrophils and monocytes play an important role in overt inflammation in chronic inflammatory joint diseases such as rheumatoid arthritis (RA). The sympathetic nervous system (SNS) inhibits many neutrophil/monocyte functions and macrophage tumor necrosis factor (TNF), but because of the loss of sympathetic nerve fibers in inflamed tissue, sympathetic control is attenuated. In this study, we focused on noradrenergic and TNF regulation of human neutrophil peptides 1-3 (HNP1-3), which are proinflammatory bactericidal alpha-defensins. Methods: Synovial tissue and cells were obtained from patients with RA and osteoarthritis (OA). By using immunohistochemistry and immunofluorescence, HNP1-3 were tracked in the tissue. With synovial cell-culture experiments and ELISA, effects of norepinephrine, TNF, and cortisol on HNP1-3 were detected. Results: HNP1-3 were abundantly expressed in the synovial lining and adjacent sublining area but not in deeper layers of synovial tissue. The human beta-defensin-2, used as control, was hardly detectable in the tissue and in supernatants. HNP1-3 double-stained with neutrophils but not with macrophages, fibroblasts, T/B lymphocytes, and mast cells. Norepinephrine dose-dependently decreased HNP1-3 levels from RA and OA cells. TNF also inhibited HNP1-3 levels from OA but not from RA cells. Cortisol inhibited HNP1-3 levels only in OA patients. A combination of norepinephrine and cortisol did not show additive or synergistic effects. Conclusions: This study demonstrated an inhibitory effect of norepinephrine on HNP1-3 of mixed synovial cells. In light of these findings, the loss of sympathetic nerve fibers with low resting norepinephrine levels might also augment the inflammatory process through HNP1-3.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SYMPATHETIC-NERVE FIBERS; POLYMORPHONUCLEAR LEUKOCYTES; HUMAN BETA-DEFENSIN-2; ALPHA-DEFENSINS; IN-VITRO; CATECHOLAMINES; MACROPHAGES; PHAGOCYTOSIS; AUGMENTS; RELEASE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I Medicine > Lehrstuhl für Orthopädie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Aug 2020 06:53 |
| Last Modified: | 12 Aug 2020 06:53 |
| URI: | https://pred.uni-regensburg.de/id/eprint/25363 |
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