Lipopolysaccharide induces substance P in sympathetic ganglia via ganglionic interleukin-1 production.
The immune cytokine interleukin-1 (IL-1) causes a pronounced elevation in substance P (SP) immunoreactivity and the mRNA coding for its preprotachykinin precursor in cultured superior cervical (sympathetic) ganglia (SCG; Jonakait and Schotland, 1990; Freidin and Kessler, 1991; Hart et al., 1991). In this study we have investigated the possibility that the SCG can respond to other immune stimulators, notably lipopolysaccharide (LPS), a product of bacterial cell walls. LPS treatment of cultured SCG resulted in a dose-dependent increase in SP. However, LPS did not induce SP in the absence of non-neuronal cells, suggesting the necessity of a non-neuronal cell-derived intermediate. Since the LPS induction of SP was partially blocked by a specific IL-1 receptor antagonist (IL-1ra) and since LPS induced approximately an 8-fold increase in mRNA coding for IL-1 itself, we concluded that IL-1 is at least one of these LPS-induced intermediates. TNF-alpha, which also raises SP levels, may be another. IL-6, which may also be increased by LPS, does not increase levels of SP. The synthetic glucocorticoid hormone dexamethasone (DEX) blocks the LPS induction of SP with a Ki approximating 8 x 10(-11) M. The inhibition is due in part to the blockade of the LPS induction of ganglionic IL-1 mRNA. Moreover, inhibition of the LPS induction of SP by indomethacin implies mediation of the effect through prostaglandins. The inhibition by indomethacin suggests a non-monocytic cell source since prostaglandins are thought to restrict the LPS induction of monocytic IL-1.(ABSTRACT TRUNCATED AT 250 WORDS)
Shadiack
A M
AM
Department of Biological Sciences, Rutgers University, Newark, NJ 07102.
Carlson
C D
CD
Ding
M
M
Hart
R P
RP
Jonakait
G M
GM
D000818:Animals; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000096:biosynthesis*; D017783:Superior Cervical Ganglion / Q000378:metabolism*
D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D015847:Interleukin-4; D013373:Substance P; D003907:Dexamethasone