Calcitonin gene-related peptide enhances cytokine-induced IL-6 production by fibroblasts.
The effect of calcitonin gene-related peptide (CGRP) was investigated on cytokine-induced IL-9 production by Swiss 3T3 fibroblasts. CGRP by itself had little effect on IL-6 production, and substantially enhanced that induced by IL-1 beta or TNF alpha at concentrations of 10(-8) M or higher. The action of CGRP was mediated by a CGRP-specific receptor. In contrast, calcitonin had no effect at all. A kinetic study of IL-6 activity in the culture supernatant showed that CGRP not only accelerated but also increased IL-6 production. Enhancement by CGRP of cytokine-dependent IL-6 production was ascribed to the increased accumulation of IL-6 mRNA. IL-1 beta-induced IL-6 production was maintained by CGRP after removal of IL1 beta. The addition of CGRP to the culture following stimulation with IL-1 beta or IL-1 beta plus CGRP decelerated the decay of IL-6 mRNA. These results indicate that the augmenting effect of CGRP is mediated, at least in part, by the stabilization of IL-6-specific mRNA.
Sakuta
H
H
Department of Zoology, Faculty of Science, Kyoto University, Japan.
Inaba
K
K
Muramatsu
S
S
D016475:3T3 Cells; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology*; D004357:Drug Synergism; D007375:Interleukin-1 / Q000502:physiology*; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D007700:Kinetics; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D015740:Calcitonin Gene-Related Peptide