Key result
Inflammatory cytokines like IL-1 beta and oncostatin M upregulate B1 receptor-mediated contractile responses and DNA synthesis in rabbit aortic smooth muscle cells.
Inflammatory cytokines upregulate kinin B1 receptor-mediated contraction and DNA synthesis in rabbit aortic smooth muscle, which may be relevant to vascular tissue repair and hypertrophic responses to injury.
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No immediate clinical implications; extends preclinical evidence linking cytokines to B1 receptor-mediated vascular responses.
In rabbit aortic rings, the contractile response to kinins is mediated by the B1 receptors for kinins; the response is upregulated from an initial null level in a time- and protein synthesis-dependent manner. Incubation (3 h) with human recombinant interleukin-1 beta (IL-1 beta) selectively amplified the contractile response to the B1 receptor agonist Sar-[D-Phe8]des-Arg9-BK, while it did not affect the contractile effect of other agents (angiotensin II, endothelin-1, phenylephrine). 2. Oncostatin M (OSM), but not macrophage migration inhibitory factor (MIF), increased the contractile response to the B1 receptor agonist, des-Arg9-bradykinin (des-Arg9-BK). 3. Cultured smooth muscle cells derived from the rabbit aorta exhibit a significant des-Arg9-BK-induced increase in [3H]-thymidine incorporation if pretreated with a cyclo-oxygenase inhibitor (diclofenac) and concomitantly treated with the cytokines IL-1 or OSM. Angiotensin II, endothelin-1 or phenylephrine, alone or in the presence of IL-1 beta, exerted little effect on DNA synthesis in these cells. 4. The pharmacological characterization of the mitogenic response to kinins using a set of agonist and antagonist analogues is consistent with mediation by B1 receptors. Des-Arg9-BK-induced DNA synthesis is suppressed by prostaglandin E2 by a prostacyclin mimetic (iloprost), by the Ser/Thr protein kinase inhibitor, H-7, and by a tyrosine kinase inhibitor (i.e. an erbstatin analogue). 5. B1 receptor-mediated responses and their capacity to be regulated by cytokines, are retained in rabbit aortic smooth muscle cells. Such responses could be relevant to tissue repair mechanisms and hypertrophic medial responses to injury in arteries.
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Lévesque et al. (1995) studied this question. Inflammatory cytokines (IL-1 beta, OSM) and kinins was evaluated on Contractile response and DNA synthesis. Inflammatory cytokines like IL-1 beta and oncostatin M upregulate B1 receptor-mediated contractile responses and DNA synthesis in rabbit aortic smooth muscle cells.
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