Substance P and capsaicin release prostaglandin E<sub>2</sub>from rat intrapulmonary bronchi

Szarek, John L.; Spurlock, B.; Gruetter, Carl A.; Lemke, Sally M.

doi:10.1152/ajplung.1998.275.5.l1006

Cited by 28 publications

(38 citation statements)

References 33 publications

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“…The absence of significant correlation might be based on the fact that PGE 2 inhibits challenges that work indirectly via neural pathways or mediator release but not those that act predominantly via a direct action on airway smooth muscle, such as histamine and metacholine [2,3]. The above theory is partially supported by previous observations that PGE 2 inhibits acetylcholine release from cholinergic nerves [25], represents the ultimate mediator of airway smooth muscle relaxation produced by activation of sensory nerve inhibitory system [26], but fails to protect against bronchoconstriction induced by methacholine [27]. Another plausible explanation might be based on the theory that the inhibitory effect of PGE 2 in histamine-induced contraction appears to be concentration-dependent [28].…”

Section: Discussionmentioning

confidence: 88%

Prostaglandin E₂in the expired breath condensate of patients with asthma

Κostikas

Papatheodorou²,

Psathakis³

et al. 2003

Eur Respir J

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Inhaled prostaglandin (PG)E 2 has been found to cause bronchodilation in asthmatics, although it does not have bronchodilative effects in normal subjects. The aim of this study was to investigate the levels of PGE 2 in the expired breath condensate of patients with asthma, the possible contribution of smoking habit to its levels and the possible relationship between PGE 2 and the degree of bronchial hyperresponsiveness, as assessed by the provocation dose of histamine causing a 20% fall in forced expiratory volume in one second (FEV1) (PD20).A total of 30 mild asthmatics (15 smokers, all steroid-naive, FEV1 88¡6 (%¡SD)) and 20 healthy control subjects (10 smokers) were studied. Histamine challenge testing was performed in all subjects and the PD20 was determined.The results showed that asthmatic smokers had significantly higher values of PGE 2 compared to asthmatic nonsmokers and control subjects (40¡21 versus 14.5¡4.5 versus 11.7¡3 pg?mL -1 , respectively). Further analysis showed that PGE 2 levels were significantly higher in asthmatic smokers compared to smoker and nonsmoker controls (40¡21 versus 11.6¡2 versus 11.7¡4 pg?mL -1 , respectively). No significant difference was observed between asthmatic nonsmokers and both control smokers and control nonsmokers. No significant correlation was found between PGE 2 levels and PD20 in all groups of asthmatics, irrespective of smoking habit.In conclusion, the elevation of prostaglandin E 2 in the expired breath condensate of patients with asthma is mainly attributed to smoking habit and prostaglandin E 2 levels do not predict the degree of bronchial hyperresponsiveness. Eicosanoids are important inflammatory mediators in asthma. These lipid mediators include leukotrienes, prostaglandins and thromboxanes. Prostaglandin (PG)E 2 is a dominant cyclooxygenase product of airway epithelium and smooth muscle, and is considered to be immunomodulatory and predominantly bronchoprotective [1]. PGE 2 inhibits both exercise-induced bronchoconstriction [2] and allergen-induced early and late asthmatic responses [3], and also prevents aspirin-induced bronchoconstriction in aspirin-sensitive asthma [4]. PGE 2 has also been shown to decrease exhaled nitric oxide [5] and to prevent the induction of inducible NO synthase in certain cell lines [6]. In vitro studies have shown that PGE 2 inhibits many inflammatory events, including mast cell mediator release and eosinophil activation [7].The measurement of markers in the expired breath condensate (EBC) has proven to be a useful noninvasive method for the assessment and monitoring of airway inflammation [8]. EBC is a simple, noninvasive technique for monitoring airway inflammation. It reflects abnormalities in markers obtained bronchoscopically, in sputum and in exhaled air [8]. Measurement of PGE 2 in EBC of asthmatic patients, when compared to normal subjects, has not shown any significant differences [9,10]. However, recent evidence suggests that cigarette smoke stimulates the formation of PGE 2 in airway macrophages [11].Despi...

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Section: Discussionmentioning

confidence: 88%

Prostaglandin E₂in the expired breath condensate of patients with asthma

Κostikas

Papatheodorou²,

Psathakis³

et al. 2003

Eur Respir J

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“…Our present findings show that HK-1 and SP signal via both NK 1 and NK 2 receptors to induce PGE 2 release in colonic mucosa. It has been previously reported that SP/NK 1 receptors causes PGE 2 release from rat intrapulmonary bronchi (Szarek et al, 1998) and porcine jejunum (Thorbøll et al, 1998). Another study has demonstrated that SP stimulates PGE 2 release in human colonic epithelial cells stably transfected with NK 1 receptors (Koon et al, 2006), but such interactions have not been extensively studied in native human intestine.…”

Section: Discussionmentioning

confidence: 99%

“…PGE 2 production is increased in IBD (Baumeister et al, 1996), and it has been suggested as a mediator and/or prognostic marker in IBD (Wierciń ska-Drapalo et al, 1999;Sheibanie et al, 2007). PGE 2 and tachykinins have two-way interactions, in that tachykinins can increase levels of PGE 2 in rat intrapulmonary bronchi (Szarek et al, 1998), whereas PGE 2 also stimulates SP release in rat sensory neurons (White, 1996). Although it is clear that abnormal levels of SP, HK-1, and PGE 2 all occur in IBD, and functional interaction between SP and PGE 2 has been reported in human colonic epithelial cells (Koon et al, 2006), a mechanistic link between HK-1 and PGE 2 production remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Hemokinin-1 Stimulates Prostaglandin E₂ Production in Human Colon through Activation of Cyclooxygenase-2 and Inhibition of 15-Hydroxyprostaglandin Dehydrogenase

Dai

Perera²,

King³

et al. 2011

J Pharmacol Exp Ther

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Hemokinin-1 (HK-1) is a newly identified tachykinin, originating from the immune system rather than neurons, and may participate in the immune and inflammatory response. In colonic mucosa of patients with inflammatory bowel disease (IBD), up-regulation of the TAC4 gene encoding HK-1 and increased production of prostaglandin E 2 (PGE 2 ) occur. Our aim was to examine the mechanistic link between human HK-1 and PGE 2 production in normal human colon. Exogenous HK-1 (0.1 M) for 4 h evoked an increased PGE 2 release from colonic mucosal and muscle explants by 10-and 3.5-fold, respectively, compared with unstimulated time controls. The HK-1-stimulated PGE 2 release was inhibited by the tachykinin receptor antagonists (and was also inhibited by the cyclooxygenase (COX)-2 inhibitor N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide) (NS-398)but not by the COX-1 inhibitor 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethylpyrazole (SC-560). A parallel study with substance P showed similar results. Molecular studies with HK-1-treated explants demonstrated a stimulatory effect on COX-2 expression at both transcription and protein levels. It is noteworthy that this was coupled with HK-1-induced down-regulation of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) mRNA and protein expression. Immunoreactivity for 15-PGDH occurred on inflammatory cells, epithelial cells, platelets, and ganglia. This finding provides an additional mechanism for HK-1-evoked PGE 2 increase, in which HK-1 may interfere with the downstream metabolism of PGE 2 by suppressing 15-PGDH expression. In conclusion, our results uncover a novel inflammatory role for HK-1, which signals via NK 1 and NK 2 receptors to regulate PGE 2 release from human colonic tissue, and may further explain a pathological role for HK-1 in IBD when abnormal levels of PGE 2 occur.

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“…SP was also shown to induce COX-2 expression and NF-kB activation in human polymorphonuclear leukocytes (21). Additionally, SP stimulated PGE 2 via NK1R in isolated rat intrapulmonary bronchi and trachea preparations (22,23) and via PGE 2 R subtype 2 in murine tracheal preparations (24). However, the interactions between SP, COX-2, and PGE 2 in inducing remote ALI after severe local burn are not known.…”

mentioning

confidence: 99%

Substance P Upregulates Cyclooxygenase-2 and Prostaglandin E Metabolite by Activating ERK1/2 and NF-κB in a Mouse Model of Burn-Induced Remote Acute Lung Injury

Sio

Ang

et al. 2010

The Journal of Immunology

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Acute lung injury (ALI) is a major cause of mortality in burn patients, even without direct inhalational injury. Identification of early mediators that instigate ALI after burn and of the molecular mechanisms by which they work are of high importance but remain poorly understood. We previously reported that an endogenous neuropeptide, substance P (SP), via binding neurokinin-1 receptor (NK1R), heightens remote ALI early after severe local burn. In this study, we examined the downstream signaling pathway following SP-NK1R coupling that leads to remote ALI after burn. A 30% total body surface area full-thickness burn was induced in male BALB/c wild-type (WT) mice, preprotachykinin-A (PPT-A) gene-deficient mice, which encode for SP, and PPT-A−/− mice challenged with exogenous SP. Local burn injury induced excessive SP-NK1R signaling, which activated ERK1/2 and NF-κB, leading to significant upregulation of cyclooxygenase (COX)-2, PGE metabolite, and remote ALI. Notably, lung COX-2 levels were abrogated in burn-injured WT mice by L703606, PD98059, and Bay 11-7082, which are specific NK1R, MEK-1, and NF-κB antagonists, respectively. Additionally, burn-injured PPT-A−/− mice showed suppressed lung COX-2 levels, whereas PPT-A−/− mice injected with SP showed augmented COX-2 levels postburn, and administration of PD98059 and Bay 11-7082 to burn-injured PPT-A−/− mice injected with SP abolished the COX-2 levels. Furthermore, treatment with parecoxib, a selective COX-2 inhibitor, attenuated proinflammatory cytokines, chemokines, and ALI in burn-injured WT mice and PPT-A−/− mice injected with SP. To our knowledge, we show for the first time that SP-NK1R signaling markedly elevates COX-2 activity via ERK1/2 and NF-κB, leading to remote ALI after burn.

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Substance P and capsaicin release prostaglandin E₂from rat intrapulmonary bronchi

Cited by 28 publications

References 33 publications

Prostaglandin E₂in the expired breath condensate of patients with asthma

Prostaglandin E₂in the expired breath condensate of patients with asthma

Hemokinin-1 Stimulates Prostaglandin E₂ Production in Human Colon through Activation of Cyclooxygenase-2 and Inhibition of 15-Hydroxyprostaglandin Dehydrogenase

Substance P Upregulates Cyclooxygenase-2 and Prostaglandin E Metabolite by Activating ERK1/2 and NF-κB in a Mouse Model of Burn-Induced Remote Acute Lung Injury

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Substance P and capsaicin release prostaglandin E2from rat intrapulmonary bronchi

Cited by 28 publications

References 33 publications

Prostaglandin E2in the expired breath condensate of patients with asthma

Prostaglandin E2in the expired breath condensate of patients with asthma

Hemokinin-1 Stimulates Prostaglandin E2 Production in Human Colon through Activation of Cyclooxygenase-2 and Inhibition of 15-Hydroxyprostaglandin Dehydrogenase

Substance P Upregulates Cyclooxygenase-2 and Prostaglandin E Metabolite by Activating ERK1/2 and NF-κB in a Mouse Model of Burn-Induced Remote Acute Lung Injury

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Substance P and capsaicin release prostaglandin E₂from rat intrapulmonary bronchi

Prostaglandin E₂in the expired breath condensate of patients with asthma

Prostaglandin E₂in the expired breath condensate of patients with asthma

Hemokinin-1 Stimulates Prostaglandin E₂ Production in Human Colon through Activation of Cyclooxygenase-2 and Inhibition of 15-Hydroxyprostaglandin Dehydrogenase