| pA2 online © Copyright 2004 The British Pharmacological Society |
062P
GKT, University of London Winter Meeting December 2003 |
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Neuropeptide
modulation of oxazolone-induced delayed-type hypersensitivity reaction
in mouse ear |
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Print abstractA range of pro- and anti-inflammatory sensory neuropeptides released from capsaicin-sensitive nerve endings are known to interact with inflammatory and immune cells. The aim of this study was to learn more about this link in oxazolone-induced delayed-type hypersensitivity (DTH) reaction in the ear of mice that included tachykinin NK1 or vanilloid TRPV1 receptor knockout (KO) mice.
BALB/c, Sv129+C57/BL/6 WT, NK1KO (Cao et al., 2000), C57/BL/6 WT and TRPV1 KO (Davis et al., 2000) mice (20-30g) were anaesthetised with ketamine (100 mg/kg i.p) or isoflurane (2%, 2% O2). Oxazolone was used on both sides of the right ear. Oxazolone solution (2%, 50 µl) was applied to the abdomen on two consecutive days and hypersensitivity responses were elicited 6 days later by oxazolone applied to the ear (2%, 15 µl). The left ear received vehicle (ethanol). Ear swelling was measured by a micrometer up to 72h. Mice were killed by cervical dislocation and histopathological changes were also investigated. Capsaicin (30 mg/kg s.c. on three consecutive days) was used to impair the function of capsaicin-sensitive sensory nerves and deplete neuropeptides. In order to examine the role of NK1 receptors, an antagonist SR140333 (240 nmol/kg, i.p. Cao et al., 2000) was administered before oxazolone.
Table 1. Effect of treatments or absence of TRPV1 and NK1 receptors on oxazolone-induced DTH. Mean ± S.E.M, n=5-8, *p<0.05, **p<0.01, ***p<0.001 vs. respective oxazolone alone treatment (ANOVA).
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Treatment
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%
increase of ear thickness
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BALB/c
DTH
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OXA
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66.7±10.5
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(24h)
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OXA
+CAPS
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132.3±12.8
*
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Pre-treatment
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||
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OXA
+SR140333
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21.1±3.9
**
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Sv129+C57BL/6
DTH
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WT
OXA
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151±17.2
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(24h)
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NK1
KO OXA
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102.5±6.9
*
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C57BL/6
DTH
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WT
OXA
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97.8±8.6
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(24h)
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TRPV1
KO OXA
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162.7±9.8
***
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The results suggest that the NK1 receptor plays a pro-inflammatory role as ear thickness was less in NK1 antagonist-treated and NK1 KO mice. Conversely responses in capsaicin pretreated mice (to deplete endogenous neuropeptides) and TRPV1 KO were increased suggesting that protective neurogenic mechanisms are stimulated via the TRPV1 receptor. Thus sensory nerves may influence hypersensitivity responses via pro- as well as anti-infammatory mechanisms.
Cao et al., (2000)
J. Immunol. 164, 5424-5429.
Davis et al. (2000) Nature 405, 183-187.
Supported by Wellcome Trust International Development Award to EP & Hungarian Research Grant OTKA T-032548.