Background and Aims: Cytokine production by resident cells of the richly innervated muscularis externa may contribute to neuromuscular changes observed during intestinal inflammation. This study investigated neurotransmitter modulation of cytokine production by intestinal smooth muscle. Methods: We measured interleukin (IL)-6 messenger RNA expression by reverse-transcription polymerase chain reaction, IL-6 by bioassay, and cyclic adenosine monophosphate by enzyme immunoassay in rat cultured intestinal smooth muscle cells exposed to IL-1β, in the presence or absence of neurotransmitters. Results: IL-1β significantly increased IL-6 messenger RNA and protein. This was dose-dependently enhanced by vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP), and norepinephrine and inhibited by [LYS1,PRO2,5,ARG3,4,TYR6]VIP and propranolol, respectively. Forskolin mimicked the stimulatory effects of these neurotransmitters on IL-6 secretion, and the protein kinase inhibitor6-22 amide abolished the actions of VIP, CGRP, and norepinephrine, but not that of human recombinant IL-1β, on IL-6 secretion. These agents each increased cyclic adenosine monophosphate activity in muscle substance P, and the neurokinin 1 agonist Ac-[Arg6,Sar9,Met(O2)11] substance P(6-11) inhibited the IL-11β-induced IL-6 release. Conclusions: This study shows neuropeptide and sympathetic modulation of IL-1β-induced IL-6 production by intestinal smooth muscle. These interactions may contribute to altered muscle function during intestinal inflammation.
Neurotransmitters modulate cytokine-stimulated interleukin 6 secretion in rat intestinal smooth muscle cells / Van Assche G.; Barbara G.; Deng Y.; Lovato P.; Gauldie J.; Collins S.M.. - In: GASTROENTEROLOGY. - ISSN 0016-5085. - ELETTRONICO. - 116:2(1999), pp. 346-353. [10.1016/S0016-5085(99)70131-9]
Neurotransmitters modulate cytokine-stimulated interleukin 6 secretion in rat intestinal smooth muscle cells
Barbara G.;Deng Y.;
1999
Abstract
Background and Aims: Cytokine production by resident cells of the richly innervated muscularis externa may contribute to neuromuscular changes observed during intestinal inflammation. This study investigated neurotransmitter modulation of cytokine production by intestinal smooth muscle. Methods: We measured interleukin (IL)-6 messenger RNA expression by reverse-transcription polymerase chain reaction, IL-6 by bioassay, and cyclic adenosine monophosphate by enzyme immunoassay in rat cultured intestinal smooth muscle cells exposed to IL-1β, in the presence or absence of neurotransmitters. Results: IL-1β significantly increased IL-6 messenger RNA and protein. This was dose-dependently enhanced by vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP), and norepinephrine and inhibited by [LYS1,PRO2,5,ARG3,4,TYR6]VIP and propranolol, respectively. Forskolin mimicked the stimulatory effects of these neurotransmitters on IL-6 secretion, and the protein kinase inhibitor6-22 amide abolished the actions of VIP, CGRP, and norepinephrine, but not that of human recombinant IL-1β, on IL-6 secretion. These agents each increased cyclic adenosine monophosphate activity in muscle substance P, and the neurokinin 1 agonist Ac-[Arg6,Sar9,Met(O2)11] substance P(6-11) inhibited the IL-11β-induced IL-6 release. Conclusions: This study shows neuropeptide and sympathetic modulation of IL-1β-induced IL-6 production by intestinal smooth muscle. These interactions may contribute to altered muscle function during intestinal inflammation.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
