Claudius U Meyer1, Gerhard Kurlemann2, Matthias Sauter3, Adelheid Wiemer-Kruel4, Andreas Hahn5, Aysefa Doganci1, Julia Birkholz1, Jörg Faber1, Stephan Gehring1, Christoph Hertzberg6, Fred Zepp1, Markus Knuf7. 1. Pediatric Immunology, Children's Hospital, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany. 2. Children's Hospital of the University Medical Center, Münster, Germany. 3. Medizinische Klinik und Poliklinik IV, Klinikum d. Universität München, Munich, Germany. 4. Epilepsy Center, Kork-Kehl, Germany. 5. Children's Hospital of the University Medical Center, Gießen, Germany. 6. DBZ, Vivantes Klinikum Neukölln, Berlin, Germany. 7. Children's Hospital of the Dr. Horst-Schmidt-Kliniken, Wiesbaden, Germany.
Abstract
OBJECTIVE: Therapeutic options for the tuberous sclerosis complex (TSC) syndrome showed varying outcomes. Malfunctional tsc1/tsc2 genes leave mTOR uninhibited, a positive downstream modulator of the innate proinflammatory immune system, which has not yet been described in pediatric patients with TSC. METHODS: Using polymerase chain reaction (PCR) gene expression levels of monocytes after cultivation with lipopolysaccharide (LPS) or with LPS + mTOR inhibitor rapamycin, patients with TSC (n = 16) were compared with healthy subjects (n = 20). RESULTS: Compared with monocytes from healthy controls, LPS showed a more prominent gene expression pattern in patients with TSC (CCL24, CXCL10, IL-6, IL-10, and IL-1B). Proinflammatory reactions against LPS were modulated by rapamycin. With LPS + rapamycin monocytes from patients with TSC showed gene expression patterns different from healthy subjects. Furthermore, developmental differences were discernible in patients with TSC, compared with gene expression levels for patients 0 to 5 years to those 6 to 11 years of age, the latter with marked expression of IL-6 IL-1A, IL-1B, RIPK2, but also IL-10. CONCLUSION: The effects of LPS, even more of LPS with rapamycin on monocytes from patients with TSC suggested that inflammatory processes are distinct from those in healthy subjects. Furthermore, reaction to rapamycin indicates age-related gene expression levels. Our findings offer a model to decipher the unknown and varying gene expression pattern induced by rapamycin. Georg Thieme Verlag KG Stuttgart · New York.
OBJECTIVE: Therapeutic options for the tuberous sclerosis complex (TSC) syndrome showed varying outcomes. Malfunctional tsc1/tsc2 genes leave mTOR uninhibited, a positive downstream modulator of the innate proinflammatory immune system, which has not yet been described in pediatric patients with TSC. METHODS: Using polymerase chain reaction (PCR) gene expression levels of monocytes after cultivation with lipopolysaccharide (LPS) or with LPS + mTOR inhibitor rapamycin, patients with TSC (n = 16) were compared with healthy subjects (n = 20). RESULTS: Compared with monocytes from healthy controls, LPS showed a more prominent gene expression pattern in patients with TSC (CCL24, CXCL10, IL-6, IL-10, and IL-1B). Proinflammatory reactions against LPS were modulated by rapamycin. With LPS + rapamycin monocytes from patients with TSC showed gene expression patterns different from healthy subjects. Furthermore, developmental differences were discernible in patients with TSC, compared with gene expression levels for patients 0 to 5 years to those 6 to 11 years of age, the latter with marked expression of IL-6IL-1A, IL-1B, RIPK2, but also IL-10. CONCLUSION: The effects of LPS, even more of LPS with rapamycin on monocytes from patients with TSC suggested that inflammatory processes are distinct from those in healthy subjects. Furthermore, reaction to rapamycin indicates age-related gene expression levels. Our findings offer a model to decipher the unknown and varying gene expression pattern induced by rapamycin. Georg Thieme Verlag KG Stuttgart · New York.