Interference of psychopharmacological agents with substance P-induced gene expression and expression of the receptor for substance P

2004 ◽  
Vol 36 (05) ◽  
Author(s):  
M von Kleinsorgen ◽  
M Hamke ◽  
Y Treffurth ◽  
M Berger ◽  
BL Fiebich ◽  
...  
2018 ◽  
Vol 115 (40) ◽  
pp. E9381-E9390 ◽  
Author(s):  
Alexandra Taracanova ◽  
Irene Tsilioni ◽  
Pio Conti ◽  
Errol R. Norwitz ◽  
Susan E. Leeman ◽  
...  

Mast cells are critical for allergic and inflammatory responses in which the peptide substance P (SP) and the cytokine IL-33 are involved. SP (0.01–1 μM) administered together with IL-33 (30 ng/mL) to human cultured LAD2 mast cells stimulates a marked increase (P< 0.0001) in secretion of the proinflammatory cytokine IL-1β. Preincubation of LAD2 (30 min) with the SP receptor (NK-1) antagonists L-733,060 (10 μM) or CP-96345 (10 µM) inhibits (P< 0.001) secretion of IL-1β stimulated by either SP (1 μM) or SP together with IL-33 (30 ng/mL). Surprisingly, secretion of IL-1β stimulated by IL-33 is inhibited (P< 0.001) by each NK-1 antagonist. Preincubation with an antibody against the IL-33 receptor ST2 inhibits (P< 0.0001) secretion of IL-1β stimulated either by IL-33 or together with SP. The combination of SP (1 μM) with IL-33 (30 ng/mL) increases IL-1β gene expression by 90-fold in LAD2 cells and by 200-fold in primary cultured mast cells from human umbilical cord blood. The combination of SP and IL-33 increases intracellular levels of IL-1β in LAD2 by 100-fold and gene expression of IL-1β and procaspase-1 by fivefold and pro-IL-1β by twofold. Active caspase-1 is present even in unstimulated cells and is detected extracellularly. Preincubation of LAD2 cells with the natural flavonoid methoxyluteolin (1–100 mM) inhibits (P< 0.0001) secretion and gene expression of IL-1β, procaspase-1, and pro-IL-1β. Mast cell secretion of IL-1β in response to SP and IL-33 reveals targets for the development of antiinflammatory therapies.


Toxicology ◽  
2004 ◽  
Vol 204 (2-3) ◽  
pp. 229-239 ◽  
Author(s):  
Stacy L. Casbohm ◽  
James V. Rogers ◽  
Mindy K. Stonerock ◽  
Jamie L. Martin ◽  
Karen M. Ricketts-Kaminsky ◽  
...  

2006 ◽  
Vol 97 (2) ◽  
pp. 397-407 ◽  
Author(s):  
V. S. Seybold ◽  
L. G. Coicou ◽  
R. D. Groth ◽  
P. G. Mermelstein

1993 ◽  
Vol 73 (1) ◽  
pp. 35-40 ◽  
Author(s):  
Stephen I. Lentz ◽  
Michael S. Poosch ◽  
Kei Hirayama ◽  
Gregory Kapatos ◽  
Michael J. Bannon

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