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Shedding of soluble receptor for tumor necrosis factor alpha induced by M. leprae or LPS from human mononuclear cells
D O Santos1, K Lorré, M de Boer
1Department of Cellular and Molecular Biology, University Federal Fluminense, Niterói, Brasil.
Abstract:
Cell surface expression and release of the tumor necrosis factor receptor (TNFR type I) was analyzed after stimulation of peripheral blood mononuclear cells (PBMC) with Mycobacterium leprae (M. leprae) or lipopolysaccharide (LPS). A transient spontaneous expression of TNFR type I on the surface of PBMC was observed. Two hr after activation with LPS, a significant reduction of TNFR type I expression was detected: Release of TNFR type I by M. leprae or LPS-stimulated PBMC was evaluated with an enzyme-linked immunoabsorbent assay. This release occurred relatively later (20 to 40 hr) than the secretion of TNF alpha which reached high levels between 8 to 20 hr after activation. Thalidomide, a potent drug for the treatment of erythema nodosum leprosum episodes by inhibiting TNF alpha production, had no influence on the TNFR type I expression. Similar results were obtained with pentoxifylline. It is concluded that the release of TNFR type I by M. leprae or LPS-stimulated PBMC may counteract the pro-inflammatory activities of TNF alpha, by reducing the systemic toxicity of this cytokine in leprosy.
Insights
Tumor necrosis factor receptor type I (TNFR type I) is released later than TNF alpha by stimulated immune cells. This release may reduce TNF alpha
Area of Science:
- Immunology
- Cell Biology
- Molecular Medicine
Background:
- Tumor necrosis factor receptor type I (TNFR type I) plays a critical role in inflammatory responses.
- Understanding TNFR type I dynamics is crucial for managing inflammatory diseases like leprosy.
Purpose of the Study:
- To analyze the cell surface expression and release of TNFR type I from peripheral blood mononuclear cells (PBMC) stimulated with Mycobacterium leprae (M. leprae) or lipopolysaccharide (LPS).
- To investigate the temporal relationship between TNFR type I release and TNF alpha secretion.
- To determine the effect of thalidomide and pentoxifylline on TNFR type I expression.
Main Methods:
- Stimulation of PBMC with M. leprae or LPS.
- Flow cytometry for cell surface expression analysis.
- Enzyme-linked immunosorbent assay (ELISA) for TNFR type I release quantification.
- Assessment of TNF alpha secretion levels.
Main Results:
- A transient spontaneous expression of TNFR type I on PBMC surface was observed.
- LPS stimulation led to a significant reduction in TNFR type I expression after 2 hours.
- TNFR type I release occurred later (20-40 hr) than TNF alpha secretion (8-20 hr).
- Thalidomide and pentoxifylline did not influence TNFR type I expression.
Conclusions:
- The release of TNFR type I by M. leprae or LPS-stimulated PBMC may counteract pro-inflammatory TNF alpha activities.
- This release mechanism could potentially reduce the systemic toxicity of TNF alpha in leprosy.
- TNFR type I dynamics represent a potential therapeutic target in inflammatory conditions.