title: [The regulative effects ofAspergillus fumigatuson expression of glucocorticoid receptor in asthmatic rats].
abstract: Objective:To study the regulative effects ofAspergillus fumigatus(A.fumigatus) on expression of glucocorticoid receptor (GCR) in asthmatic rats.Methods:Wistar rats were randomly divided into 4 groups: a normal control group (UC), a normal control withA.fumigatusgroup (UC+ AF), an OVA group (OVA), and an OVA withA.fumigatusgroup (OVA+ AF). OVA and OVA+ AF groups were sensitized and challenged with OVA to establish asthmatic models. UC and UC+ AF groups were given normal saline as controls. After the last challenge, OVA+ AF and UC+ AF groups were givenA.fumigatusspores intranasally. Airway hyper-responsiveness, eosinophil percentage (Eos%) and serum IgE level were measured to confirm the establishment of asthmatic models. Sections of pulmonary tissue were stained with hematoxylin-eosin (HE) and the expression of GCR mRNA and protein in lung tissues were measured by qRT-PCR and Western blot. Lung tissues and blood were plated on the potato dextrose agar(PDA)medium and cultured for 24 h to measure the number of colony.Results:The Penh value, Eos% in BALF and serum IgE level in UC+ AF group were slightly higher than those in the UC group (all theP>0.05). The Penh value, Eos% in BALF and serum IgE level in OVA group were significantly higher than those in the UC group (all theP<0.05). The Penh value in OVA+ AF group was significantly increased compared with the OVA group at the concentration of 25 g/L and 50 g/L of methacholine (all theP>0.05). Pulmonary histology revealed that both OVA group and OVA+ AF group showed high levels of inflammatory cell infiltration of bronchus and lung vessels, interstitial edema and smooth muscle thickening, while the UC and UC + AF groups were normal. Compared with the UC group, the expressions of GCR mRNA and protein in UC+ AF group and OVA group were decreased significantly (GCR mRNA in UC, UC+ AF and OVA group were 0.93±0.15, 0.65±0.10, 0.72±0.22, respectively,F=10.744,P<0.01; GCR protein in UC, UC+ AF and OVA group were 100±0, 89±8, 82±15, respectively,F=18.939,P<0.01). The expressions of GCR mRNA and protein in OVA+ AF group were further decreased than those in OVA group (GCR mRNA: OVA group: 0.72±0.22 vs OVA+ AF group: 0.52±0.08,t=2.462,P<0.05; GCR protein: OVA group: 81.88±15.41 vs OVA+ AF group: 59.09±7.60,t=2.997,P<0.05). The ratio ofA.fumigatuscolonization in lung tissues in OVA+ AF group (4/8) was higher than the UC+ AF group (0/8).Conclusion:A.fumigatusexposure can down-regulate the expression of GCR in the lung, which maybe an important mechanism of steroid-resistant asthma.
authors.affiliation: Department of Respiratory Medicine, Huashan Hospital Affiliated to Fudan University, Shanghai 200040, China.
authors.forename: X
authors.initials: X
authors.lastname: Zhou
authors.forename: Y J
authors.initials: YJ
authors.lastname: Dang
authors.forename: G F
authors.initials: GF
authors.lastname: Wang
authors.forename: X Q
authors.initials: XQ
authors.lastname: Jin
mesh_terms: D000818:Animals; D001232:Aspergillus fumigatus; D001249:Asthma / Q000378:metabolism*; D001980:Bronchi; D001992:Bronchoalveolar Lavage Fluid; D007958:Leukocyte Count; D008168:Lung / Q000378:metabolism* / Q000382:microbiology; D008807:Mice, Inbred BALB C; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000378:metabolism*
chemical_list: D011965:Receptors, Glucocorticoid
keywords: Aspergillus fumigatus; Asthma; Receptors, glucocorticoid