ABSTRACT
Objective@#To study the effect of dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis on the pathogenesis of allergic rhinitis (AR) by the mouse model of decreased endogenous glucocorticoid (GC) after adrenalectomy, and further explore the mechanism of neural-endocrine regulation.@*Methods@#According to literatures, adrenalectomized (ADX) mice and AR model were established. Eighty mice were randomly divided into four groups (n=20 per group) including control group, AR group of normal mice (AR group), AR group of bilateral ADX (bilateral ADX/AR group) and AR group of unilateral ADX (unilateral ADX/AR group). In order to assess the model of ADX, adrenal gland tissue was assayed by HE staining and the plasma adrenocorticotropic hormone (ACTH) and cortisol (CORT) concentrations were measured by enzyme-linked immunosorbent assay (ELISA). The behavioral observation, OVA-sIgE assessments and count of eosinophils/mast cells by the HE/Toluidine Blue staining of nasal septum mucosa tissue were performed to evaluate the AR model. The expression of peripheral blood CD4+ IL4+ T cells (Th2 cells) and CD4+ IFN-γ+ T cells (Th1 cells), splenocytes of CD4+ CD25+ Treg cells (Treg cells) were measured by flow cytometry to study the influence of endogenous GC on immunological indexes in different groups of mice. SPSS 16.0 software was used to analyze the data.@*Results@#The concentrations of OVA-sIgE in control group, AR group, bilateral ADX/AR group and unilateral ADX/AR group mice were (28.86±3.62) ng/ml, (76.27±16.47) ng/ml, (48.37±8.89) ng/ml, (49.86±7.19) ng/ml, respectively. There was statistically significant difference between control group and AR group (t=7.09, P<0.05), AR group and bilateral ADX/AR group (t=4.81, P<0.05), AR group and unilateral ADX/AR group (t=5.21, P<0.05). The level of Th2 cells in different four groups were (0.71±0.24)%, (7.03±1.95)%, (2.44±2.06)%, (3.20±1.21)%, respectively. There was statistically significant difference between control group and AR group (t=-2.93, P<0.05), AR group and bilateral ADX/AR group (t=-4.67, P<0.05), AR group and unilateral ADX/AR group (t=-3.61, P<0.05). The expression of Th2 in bilateral ADX/AR group is lower than that in unilateral ADX/AR group without significant difference (t=4.39, P>0.05). Meanwhile, the level of Th1 cells in different four groups was (0.58±0.76)%, (0.57±0.59)%, (0.72±0.34)%, (1.03±0.32)%, respectively, with no significant difference among these groups. The proportion of Treg cells was (11.10±2.18)%, (4.10±1.07)%, (7.15±0.92)%, (4.58±1.05)%, respectively, with significant difference between control and other groups (t value was -7.171, -8.273, -8.360, respectively, all P<0.05). Compared with AR group, Treg cells increased significantly in bilateral ADX/AR group (t=-2.607, P<0.05). In addition, lower expression of eosinophil and mast cell were detected in the local nasal tissue of bilateral ADX/AR group, and mast cell degranulation wasn′t be observed.@*Conclusion@#Unilateral or bilateral ADX leads to HPA axis dysfunction and endogenous GC deprivation, possibly regulating the mechanism of AR through Th1/Th2 immune bias and Tregs cell′ activity.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the role of TIM4 (T cell immunoglobulin and mucin domain molecule 4) in the pathogenesis of allergic rhinitis (AR) in mice, and to identify a novel therapeutic target for the treatment of AR.</p><p><b>METHODS</b>Twenty-one male BALB/C mice of clean grade were divided into three groups randomly (n = 7 per group) including control, AR and anti-TIM4 antibody treatment groups. In order to induce upper airway allergic inflammation, the mice from AR and anti-TIM4 antibody treatment groups were sensitized by intraperitoneal injection followed by intranasal challenge with ovalbumin. Before the ovalbumin challenge, a group of mice was treated with anti-TIM4 antibody. To assess the AR model, behavioral observation with immunological assessments and HE staining of nasal tissues were performed. The TIM4 expression in nasal tissues in different groups of mice were assessed by immunofluorescence and RT-PCR.SPSS18.0 software was used to analyze the data.</p><p><b>RESULTS</b>The AR model in mice was successfully established as shown by behavioral observation and immunological evaluation. RT-PCR assays showed the relative expression of TIM4 mRNA in nasal mucosa of AR, control and anti-TIM4 antibody treatment mice was 16.29 ± 3.80, 0.51 ± 0.60, 1.64 ± 0.98, respectively. There was statistically significant differences mong three group (F = 46.56, P < 0.05). The expression of TIM4 in AR group was significantly higher than those in control group (t = 8.650, P < 0.05) and anti-TIM4 group (t = 8.027, P < 0.05). The expression of TIM4 was significantly reduced in the anti-TIM4 antibody group, as well as control group (t = -0.623, P > 0.05). More expression of TIM4 was detected in local nasal tissues of AR mice, mainly located below the pseudostratified ciliated columnar epithelium.</p><p><b>CONCLUSIONS</b>TIM4 plays a crucial role in the pathogenesis of AR. Effective inhibition of TIM4 expression can partially reverse the pathological changes of AR.</p>