Effects of Some Natural Carotenoids on TRPA1- and TRPV1-Induced Neurogenic Inflammatory Processes In Vivo in the Mouse Skin
- 449 Downloads
Mechanisms of the potent anti-inflammatory actions of carotenoids are unknown. Since carotenoids are incorporated into membranes, they might modulate transient receptor potential ankyrin 1 and vanilloid 1 (TRPA1 and TRPV1) activation predominantly on peptidergic sensory nerves. We therefore investigated the effects of three carotenoids (β-carotene, lutein and lycopene) on cutaneous neurogenic inflammation. Acute neurogenic edema and inflammatory cell recruitment were induced by smearing the TRPA1 agonist mustard oil (5 %) or the TRPV1 activator capsaicin (2.5 %) on the mouse ear. Ear thickness was then determined by micrometry, microcirculation by laser Doppler imaging and neutrophil accumulation by histopathology and spectrophotometric determination of myeloperoxidase activity. The effects of lutein on the stimulatory action of the TRPA1 agonist mustard oil were also tested on the guinea-pig small intestine, in isolated organ experiments. Mustard oil evoked 50–55 % ear edema and granulocyte influx, as shown by histology and myeloperoxidase activity. Swelling was significantly reduced between 2 and 4 h after administration of lutein or β-carotene (100 mg/kg subcutane three times during 24 h). Lutein also decreased neutrophil accumulation induced by TRPA1 activation, but did not affect mustard oil-evoked intestinal contraction. Lycopene had no effect on any of these parameters. None of the three carotenoids altered capsaicin-evoked inflammation. It is proposed that the dihydroxycarotenoid lutein selectively inhibits TRPA1 activation and consequent neurogenic inflammation, possibly by modulating lipid rafts.
KeywordsMustard oil Transient receptor potential (TRP) vanilloid 1 ion channel (TRPV1) TRPA1 receptor Carotenoids Skin inflammation Intestinal contraction Lipid rafts
The authors thank Anikó Hirné Perkecz for the preparation of the histological slides and Dániel Tóth and Veronika Szombati for technical assistance. The research was supported by SROP-4.2.2.A-11/1/KONV-2012-0024 and Hungarian Brain Research Program KTIA_NAP_13-1-2013-0001. József Deli was supported by OTKA K 83898 grant (Hungarian Scientific Research Fund). We thank Prof. George Britton for the language correction and thank Dr. István Juricskay for the statistical analysis.
Conflict of Interest
The authors declare that there are no conflicts to disclose.
- Britton G (1995) Procedure: isolation of carotenes from tomato fruit. In: Britton G, Liaaen-Jensen S, Pfander H (eds) Carotenoids, vol. 1A. Birkhäuser Verlag, Basel, pp 210–213Google Scholar
- Britton G, Liaaen-Jensen S, Pfander H (1995) Carotenoids today and challenges for the future. In: Britton G, Liaaen-Jensen S, Pfander H (eds) Carotenoids, vol. 1A. Birkhäuser Verlag, Basel, pp 13–26Google Scholar
- Helyes Z, Pintér E, Németh J, Szolcsányi J (2003) Pharmacological targets for the inhibition of neurogenic inflammation. AIAAA in Curr Med Chem 2:191–218Google Scholar
- Helyes Z, Pintér E, Szolcsányi J (2009) Regulatory role of sensory neuropeptides in inflammation. In: Kovács M, Merchenthaler I (eds) Neuropeptides and peptide analogs, vol. 7. Research Signpost, Kerala, pp 111–141Google Scholar
- Molnár P, Kawase M, Motohashi N (2005) Isolation, crystallization and handling of carotenoids and (E/Z)-isomerization of carotenoids. In: Motohashi N (ed) Functional polyphenols and carotenoids with antioxidative action, a review book series of Chem. Pharm. Sci. RSFLASH, Kerala, pp 111–131Google Scholar
- Schiedt K, Liaaen-Jensen S (1995) Isolation and analysis. In: Britton G, Liaaen-Jensen S, Pfander H (eds) Carotenoids, vol. 1A. Birkhäuser Verlag, Basel, pp 109–144Google Scholar