Substance P gene expression is regulated by interleukin‐1 in cultured sympathetic ganglia

Hart, Ronald P.; Shadiack, Annette M.; Jonakait, G. Miller

doi:10.1002/jnr.490290303

Cited by 75 publications

(29 citation statements)

References 83 publications

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“…IL-1p regulates substance P levels in sympathic ganglion cells (Hart et al, 1991) through the induction of a neuropoietic cytokine leukaemia inhibitory factor (LIF) (Shadiack et al, 1993). IL-P could alter neuropeptide expression in primary sensory neurones secondary to an increase in NGF levels since NGF has well known actions on the regulation of both substance P and CGRP in adult DRG neurones (Lindsay & Harmar, 1989;Woolf et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

Contribution of interleukin‐1β to the inflammation‐induced increase in nerve growth factor levels and inflammatory hyperalgesia

Safieh‐Garabedian

Poole

Allchorne

et al. 1995

British J Pharmacology

550

324

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Peripheral inflammation is associated with the local production of neuroactive inflammatory cytokines and growth factors. These may contribute to inflammatory pain and hyperalgesia by directly or indirectly altering the function or chemical phenotype of responsive primary sensory neurones. To investigate this, inflammation was produced by the intraplantar injection of complete Freund's adjuvant (CFA) in adult rats. This resulted in a significant elevation in interleukin‐ip (IL‐1β) and nerve growth factor (NGF) levels in the inflamed tissue and of the peptides, substance P and calcitonin gene‐related peptide (CGRP) in the L4 dorsal root ganglion 48 h post CFA injection. The effects of a steroidal (dexamethasone) and a non‐steroidal (indomethacin) anti‐inflammatory drug on the levels of NGF and IL‐1β in inflamed tissue were investigated and compared with alterations in behavioural hyperalgesia and neuropeptide expression in sensory neurones. Systemic dexamethasone (120 μg kg−1 per day starting the day before the CFA injection) had no effect on the inflammatory hyperalgesia. When the dose was administered 3 times daily, a reduction in mechanical and to a lesser extent thermal sensitivity occurred. Indomethacin at 2 mg kg−1 daily (i.p.) had no effect on the hyperalgesia and a dose of 4 mg kg−1 daily was required to reduce significantly mechanical and thermal hypersensitivity. The increase in NGF produced by the CFA inflammation was prevented by both dexamethasone and indomethacin, but only at the higher dose levels. Dexamethasone at the lower and higher dose regimes diminished the upregulation of IL‐1β whereas indomethacin had an effect only at the higher dose. The increase in SP and CGRP levels produced by the CFA inflammation was prevented by dexamethasone and indomethacin at the lower and higher dose regimes. Intraplantar injections of IL‐1β (0.01, 0.1 and 1 ng) produced a brief (6 h) thermal hyperalgesia and an elevation in cutaneous NGF levels which was prevented by pretreatment with human recombinant IL‐1 receptor antagonist (IL‐1 ra) (0.625 μg, i.v.). The thermal hyperalgesia but not the NGF elevation produced by intraplantar IL‐1β (1 ng) was prevented by administration of a polyclonal neutralizing anti‐NGF serum. IL‐1 ra significantly reduced the mechanical hyperalgesia produced by CFA for 6 h after administration as well as the CFA‐induced elevation in NGF levels. Anti‐NGF pretreatment substantially reduced CFA‐induced mechanical and thermal hyperalgesia without reducing the elevation in IL‐1β. Intraplantar NGF (0.O2, 0.2 and 2 μg) injections produced a short lasting thermal and mechanical hyperalgesia but did not change IL‐1β levels in the hindpaw skin. Our results demonstrate that IL‐1β contributes to the upregulation of NGF during inflammation and that NGF has a major role in the production of inflammatory pain hypersensitivity.

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Section: Discussionmentioning

confidence: 99%

Contribution of interleukin‐1β to the inflammation‐induced increase in nerve growth factor levels and inflammatory hyperalgesia

Safieh‐Garabedian

Poole

Allchorne

et al. 1995

British J Pharmacology

550

324

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“…PPT-I is expressed with different efficiency and by different stimuli in particular tissues (1,5,11). In BM stromal cells, although macrophage and fibroblasts express endogenous PPT-I when stimulated by IL-1␣, the levels in macrophage are relatively higher than fibroblasts (data not shown).…”

Section: Cell-specific Activity Of Ppt-i Promotermentioning

confidence: 92%

Cloning of Human Preprotachykinin-I Promoter and the Role of Cyclic Adenosine 5′-Monophosphate Response Elements in Its Expression by IL-1 and Stem Cell Factor

Qian¹,

Yehia

Molina

et al. 2001

The Journal of Immunology

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Preprotachykinin-I gene (PPT-I) encodes several peptides with organ-specific functions that link the neuroendocrine-immune-hemopoietic axis. We cloned upstream of the initiation site of human PPT-I promoter and identified consensus sequences for two cAMP response elements (CRE). PPT-I is induced by cytokines including those that signal through the cAMP pathway. Therefore, we studied the role of the two CRE in IL-1α and stem cell factor (SCF) stimulation of bone marrow stroma because both cytokines induce endogenous PPT-I in these cells and activate the cAMP pathway. Furthermore, bone marrow stroma expresses the transcription factors regulated by the cAMP pathways such as the repressor (ICERIIγ) and activator (CREMτ). Mutagenesis of the two CRE and/or cotransfection with vectors that express ICERIIγ or CREMτ indicated that the two CRE have major roles in PPT-I expression. The two CRE are also required for optimal promoter activity by SCF and IL-1α. A particular cytokine could concomitantly induce PPT-I and the high affinity G protein-coupled receptor for PPT-I peptides, NK-1R. We showed that SCF, a representative cytokine, induced PPT-I and NK-1R leading to autocrine and/or paracrine cell activation. Because NK-1R activates cAMP through the G protein, the results suggest that the presence of CRE sequences within PPT-I promoter could be important in the regulation of PPT-I expression by cytokines, irrespective of their ability to signal through cAMP. As PPT-I is implicated in hemopoietic regulation, immune responses, breast cancer, and other neural functions, these studies add to the basic biology of these processes and could provide targets for drug development.

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“…Mutual interactions between TNF-α and tachykinins have been described in different models 39 and TNF-α was shown to induce SP expression by sympathetic ganglia: 40 since TNF-α is reduced in MO from smokers, 34 this cytokine could be implicated. Moreover, a recent paper by Emms and Rogers 41 demonstrates that, in the guineapig, cigarette smoke exposure reduced the magnitude of subsequent bronchoconstriction induced by NKA by 40%, in keeping with the results reported here.…”

Section: Effects Of Tachykinin Selective Antagonists On Superoxide Anmentioning

confidence: 99%

Tachykinin activation of human monocytes from patients with interstitial lung disease, healthy smokers or healthy volunteers

et al. 2000

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Summary Three types of tachykinin receptors, NK 1 , NK 2 and NK 3 , have been described to preferentially interact with substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) respectively. Experimental evidence indicates that SP and NKA modulate the activity of inflammatory and immune cells, including mononuclear ones, and points to their involvement in lung pathophysiology. We previously reported that NK 1 and NK 2 receptors are present on monocytes (MO) isolated from healthy donors or rheumatoid patients -a greater sensitivity to NK 2 receptor stimulation was observed in the latter condition. This study evaluated the effects of SP and NKA, as well as NK 1 and NK 2 selective agonists and antagonists, on MO obtained from healthy volunteers, healthy smokers or patients with interstitial lung diseases (e.g. sarcoidosis and idiopathic pulmonary fibrosis). Superoxide anion (O 2 -) production was chosen as a parameter of cell activation. SP and NKA dose-dependently evoked O 2 -production from MO in all the conditions evaluated, their effects being competitively antagonized by selective antagonists (CP 96 345 and MEN 10 627, respectively). When selective NK 1 and NK 2 agonists were used, [Sar 9 Met(O 2 ) 11 ]SP, a selective NK 1 agonist, induced a more than doubled O 2 production in MO obtained from patients with interstitial lung diseases as compared to healthy volunteers, whereas MO isolated from healthy volunteers were more sensitive to NK 2 receptor stimulation.

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Substance P gene expression is regulated by interleukin‐1 in cultured sympathetic ganglia

Cited by 75 publications

References 83 publications

Contribution of interleukin‐1β to the inflammation‐induced increase in nerve growth factor levels and inflammatory hyperalgesia

Contribution of interleukin‐1β to the inflammation‐induced increase in nerve growth factor levels and inflammatory hyperalgesia

Cloning of Human Preprotachykinin-I Promoter and the Role of Cyclic Adenosine 5′-Monophosphate Response Elements in Its Expression by IL-1 and Stem Cell Factor

Tachykinin activation of human monocytes from patients with interstitial lung disease, healthy smokers or healthy volunteers

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