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F. Zhang, J. E. Capo-Aponte, Z. Wang, H. Yang, Z. Pan, H. Liu, S. Mergler, P. S. Reinach; Transient Receptor Potential Vanilloid 1 (TRPV1) Activation Induces Proinflammatory Responses Through MAPK Stimulation. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2824.
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© ARVO (1962-2015); The Authors (2016-present)
TRPV1 is a vanilloid subtype of the transient receptor potential protein superfamily. This isoform is a subunit of a non-selective cation channel mediating downstream responses to heat, low pH, or noxious stimuli. TRPV1 expression has been recently described in some epithelial tissues and induces proinflammatory cytokine release through mitogen-activated protein kinase (MAPK) superfamily stimulation. We describe here in human corneal epithelial cells (HCEC) the signaling pathways mediating TRPV1-induced increases in proinflammatory cytokine release.
Immunohistology, immunocytochemistry and Western Blot analysis identified TRPV1 expression in intact human corneal epithelium, primary and SV40-immortalized human corneal epithelial cells (pHCEC and HCEC, respectively). The effects of the TRPV1 agonist, capsaicin (CAP), on MAPK superfamily activation were evaluated by Western Blot analysis. ELISA quantified CAP-induced increases in proinflammatory cytokine (i.e.IL-8 and IL-6) release. The involvement of p38 JNK and ERK MAPK branches were evaluated based on the relative inhibitory effects of specific MAPK inhibitors: 10 µM SB203580, 10 µM SP600125 and 10 µM U0126, respectively on these responses.
TRPV1 expression was detected in pHCEC, HCEC and the intact human corneal epithelium. In HCEC, TRPV1 staining was delimited to the cell margins. CAP(1 µM) induced after 5 min maximal global p38 MAPK, JNK and Erk1/2 activation. Over the next 90 min, such stimulation gradually waned towards their baseline values. p38 MAPK was maximally activated by all CAP concentrations (i.e.0.5-100 µM). On the other hand, maximal JNK and Erk1/2 activation occurred with 10 µM and 0.1 µM CAP, respectively. Pretreatment with the TRPV1 receptor antagonist capsazepine (CPZ) blocked its activation. CAP (1 µM) maximally increased IL-8 and IL-6 8- and 4- fold release, respectively. Such rises were completely suppressed by CPZ (10 µM) whereas they were only partially suppressed by either SB203580, SP600125 or U0126.
TRPV1 receptor stimulation in HCEC induces through three MAPK limbs increases in proinflammatory cytokine release. These results suggest that epithelial TRPV1 expression contributes in-vivo to mounting proinflammatory reactions to noxious stimuli.
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