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Objective@#To explore the effect of neurokinin-1 receptor small interfering RNA (NK-1R-siRNA) on the expression of inflammation factors in allergic rhinitis (AR).@*Methods@#Twenty-four male SD rats were divided into three groups randomly (by random number table methord): NK-1R-siRNA group, negative control siRNA (NC-siRNA) group and saline group, with 8 rats in each group. SD rats were sensitized and challenged with ovalbumin (OVA) to induce AR. The rats were treated intranasally with NK-1R-siRNA, NC-siRNA or saline before and during the challenge period. The AR symptoms were observed. The levels of OVA-specific IgE were measured by enzyme-linked immunosorbent assay (ELISA). The levels of NK-1R expression in the nasal mucosal tissues were determined by real time PCR (RT-PCR) and immunohistochemistry. Antibody array was used in studying the expression of inflammation cell factors in nasal mucosa. SPSS 11.0 software was used for one-factor analysis of variance.@*Results@#Compared with saline group, AR symptoms relived significantly in NK-1R-siRNA group (nose rubbing (31.4±8.9)/15 min vs (69.5±17.9)/15 min, sneezing (7.2±1.9)/15 min vs (23.7±9.2)/15 min, nasal secretions (7.1±2.3) mg vs (24.1±4.4) mg, t value was 38.100, 17.125, 16.837, respectively, all P<0.01), and the level of serum OVA-specific IgE was also reduced ((8.56±0.73) ng/ml vs (18.05±1.22) ng/ml, t=9.787, P<0.01). The RT-PCR and immunohistochemistry results showed that the expression of NK-1R in nasal mucosa of NK-1R-siRNA group was remarkably reduced than that of the NC-siRNA group and saline group. After the treatment of NK-1R-siRNA, the expression of interleukin (IL) 1α, IL-1β, IL-4, IL-6 and IL-13 decreased, while the interferon-γ (IFN-γ) and IL-10 increased.@*Conclusion@#NK-1R-siRNA could regulate the release of inflammation factors in AR nasal mucosa, thus relive the allergic inflammation.
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Objective To investigate the expressions of substance P(SP)and neurokinin receptor(NK1R)in eosinophil-enriched cells from patients with atopic dermatitis(AD)so as to elucidate their possible roles in AD. Methods Blood samples were collected from healthy controls(HCs)and AD patients,and incubated with the extracts of Artemisia pollen,dust mite,and Platanus pollen for 1 h.The expressions of SP and NK1R in eosinophil-enriched cells were detected by flow cytometry.Results Level of NK1R in eosinophil-enriched cells from AD patients increased by 41% compared with that of HCs when cultured with the medium only(P= 0.001).In addition,the expression of SP in AD patients decreased by 1.17 folds(P＜0.001),and mean fluorescence intensity (MFI)of SP+eosinophils decreased by 55%(P＜0.001).However,allergens had little effect on the expressions of SP and NK1R in eosinophil-enriched cells from AD patients and HCs.Conclusion Upregulated expression of NK1R in AD indicates that eosinophil-derived NK1R may play an important role in AD.Antagonists or blockers of NK1R might be effective preparations for AD treatment.
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Objective The aim of this study was to investigate the mechanism underlying pruritus by comparing the epidermal growth factor receptor inhibitor(EGFRI)-erlotinib mouse model with the substance P(SP)-induced pruritus mouse model. Methods Two randomized groups of mice were treated with erlotinib or SP to induce pruritus. Behavioral and skin manifestations were observed. Pathological images and neurokinin 1 receptor(NK-1R)expression of the skin were determined. Concentration of interleukin(IL)-31, IL-33, histamine, leukotriene B4, and SP was analyzed by enzyme-linked immunosorbent assay. Nitric oxide was analyzed by colorimetry. Results Transient pruritus induced by erlotinib appeared 2 to 5 days after treatment. In contrast, continuous pruritus was observed during the first hour, but was then gradually relieved. These two shared similar scratching behavior. Concentration of neurotransmitters showed similar trends in changes among the erlotinib group and SP group. Immunohistochemical expression was also consistent between the erlotinib group and SP group. Conclusions Erlotinib-associated pruritus is related to release of signaling factors through the SP/NK-1R signaling pathway.