Evidence for a novel protective role of the vanilloid TRPV1 receptor in a cutaneous contact allergic dermatitis model Ágnes Bánvölgyi, László Pálinkás,

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Presentation transcript:

Evidence for a novel protective role of the vanilloid TRPV1 receptor in a cutaneous contact allergic dermatitis model Ágnes Bánvölgyi, László Pálinkás, Tímea Berki, Natalie Clark, Andrew D. Grant, Zsuzsanna Helyes, Gábor Pozsgai, János Szolcsányi, Susan D. Brain, Erika Pintér Journal of Neuroimmunology Volume 169, Issue 1, Pages 86-96 (December 2005) DOI: 10.1016/j.jneuroim.2005.08.012 Copyright © 2005 Elsevier B.V. Terms and Conditions

Fig. 1 Time course of ear swelling in oxazolone-induced contact dermatitis in (a) BALB/c, (b) C57BL/6 and (c) Sv127+C57BL/6 mouse strains. Animals were sensitized on two consecutive days by smearing 2% oxazolone on the shaved abdomen. On the 6th day right ears were smeared with 2% oxazolone dissolved in 96% ethanol (closed circles). Left ears were treated with 96% ethanol in the same way (open squares). Measurements were performed 24, 48 and 72 h after challenge. Comparisons between treated and non-treated animals were made by ANOVA followed by Dunnett's post-test for edema data. Values are shown as % increase of ear thickness compared with ethanol treatment. Means±SEM, n=5–7 per group, *P<0.05 vs. ethanol, **P<0.01 vs. ethanol, ***P<0.001 vs. ethanol treatment. Journal of Neuroimmunology 2005 169, 86-96DOI: (10.1016/j.jneuroim.2005.08.012) Copyright © 2005 Elsevier B.V. Terms and Conditions

Fig. 2 Effect of depletion or removal of sensory neurogenic components in oxazolone-induced ACD. ACD-induced swelling is shown in RTX-pretreated wild-type (open square) and TRPV1 knockout (closed square) C57/BL6 mice. Measurements were performed 24, 48 and 72 h after challenge. Data were expressed as % change from oxazolone-induced control. n=5–7, *P<0.05, **P<0.01, versus respective control, +P<0.05, ++P<0.001 versus respective control. Journal of Neuroimmunology 2005 169, 86-96DOI: (10.1016/j.jneuroim.2005.08.012) Copyright © 2005 Elsevier B.V. Terms and Conditions

Fig. 3 Representative light micrographs of ACD. (a) Ethanol-treated control ear in BALB/c mouse, (b) oxazolone-treated ear in BALB/c mouse, (c) oxazolone-treated C57BL/6 wild-type and (d) TRPV1 knockout mouse ear (100×). Accumulated myeloid cells were stained with naphtol AS-D chloroacetate-esterase. Journal of Neuroimmunology 2005 169, 86-96DOI: (10.1016/j.jneuroim.2005.08.012) Copyright © 2005 Elsevier B.V. Terms and Conditions

Fig. 4 Effects of the chemical and genetic modulation of sensory neurogenic pathway on neutrophil accumulation in ACD induced by oxazolone. Results are shown as MPO content of BALB/c, C57BL/6, C57BL/6+Sv126 mouse ears, after ethanol (white bars), or oxazolone treatment (black bars). Striped columns demonstrate the oxazolone effect on BALB/c or C57BL/6 mice after RTX pretreatment. Measurements were performed 48 h after challenge. Data are expressed in MPO content per ear. Values are means±SEM. n=5. Journal of Neuroimmunology 2005 169, 86-96DOI: (10.1016/j.jneuroim.2005.08.012) Copyright © 2005 Elsevier B.V. Terms and Conditions

Fig. 5 Local cytokine profile of ear tissue. Samples were collected after 24 h (a,c) and 48 h (b,d) in oxazolone-induced ACD from C57BL/6 wild-type and TRPV1 knockout (a,b) and from BALB/c (c,d) mice. Comparisons between knockout and wild-type mice or RTX-treated and non-treated animals were made by ANOVA followed by Dunnett's post-test for edema data. Values are means±SEM, n=4 per group, *P<0.05 vs. wild-type. Journal of Neuroimmunology 2005 169, 86-96DOI: (10.1016/j.jneuroim.2005.08.012) Copyright © 2005 Elsevier B.V. Terms and Conditions

Fig. 6 (a) Effect of the pretreatment with an NK1 receptor antagonist SR140333 and genetic depletion of NK1 receptor in oxazolone-induced ACD compared to positive controls; (b) effect of the removal of αCGRP in oxazolone-induced ACD compared to the wild-type controls. Measurements were performed 24, 48 and 72 h after challenge. Values are expressed in % inhibition compared to the respective oxazolone-treated control groups. n=8–10 *P<0.05, **P<0.01, ***P<0.001 vs. wild-type animals. Journal of Neuroimmunology 2005 169, 86-96DOI: (10.1016/j.jneuroim.2005.08.012) Copyright © 2005 Elsevier B.V. Terms and Conditions

Fig. 7 Local cytokine profile of ear tissue. Samples were collected after 24 h (a,c) and 48 h (b,d) in oxazolone-induced ACD from Sv129+C57BL/6 wild-type and NK1 receptor knockout (a,b) or from C57BL/6 wild-type and αCGRP knockout animals (c,d). Comparisons between knockout and wild-type mice were made by ANOVA followed by Dunnett's post-test for edema data. Values are means±SEM, n=4 per group, *P<0,05 vs. wild-type. Journal of Neuroimmunology 2005 169, 86-96DOI: (10.1016/j.jneuroim.2005.08.012) Copyright © 2005 Elsevier B.V. Terms and Conditions