Biomedical subjects

Motonori Fukakusa

Publications and source records attributed to Motonori Fukakusa.

3 recordsLinked to original sources

PubMed2005

Oral corticosteroids decrease eosinophil and CC chemokine expression but increase neutrophil, IL-8, and IFN-gamma-inducible protein 10 expression in asthmatic airway mucosa.

BACKGROUND: Cytokines and chemokines have been implicated in the pathogenesis of asthma. Inhaled corticosteroids have been shown to decrease the number of eosinophils and to downregulate T H 2 cytokines but to increase neutrophils. The effect of corticosteroids on chemokine expression in asthma has not yet been investigated. OBJECTIVE: We sought to investigate the effect of a 2-week course of oral corticosteroid (methylprednisolone, 40 mg/d) on the expression of CXC chemokines (IL-8 and IFN-gamma-inducible protein 10 [IP-10]) and CC chemokines (eotaxin and monocyte chemotactic proteins [MCPs] 1-4) in endoscopic biopsy specimens of 13 patients with moderate-to-severe asthma. METHODS: CD3, major basic protein, and elastase immunoreactivities were monitored before and after treatment by using immunocytochemistry. Eotaxin, IL-8, IP-10, MCP-1, MCP-2, MCP-3, and MCP-4 mRNA expression in epithelium and submucosa were studied by using in situ hybridization. RESULTS: Corticosteroids reduced the number of CD3-positive T cells and major basic protein-positive eosinophils ( P < .05), whereas the number of neutrophils were increased ( P < .05). Corticosteroids also reduced the number of eotaxin ( P < .05), MCP-3, and MCP-4 mRNA-positive cells ( P < .001) in the epithelium and subepithelium. However, corticosteroids caused a significant increase in the epithelial expression of IL-8 ( P < .001), IP-10 ( P < .05), and MCP-2 mRNAs ( P < .01). Corticosteroids had no effects on MCP-1 mRNA expression. CONCLUSION: Our results demonstrate the dual nature of corticosteroids. Although corticosteroids can downregulate the expression of some asthma-associated chemokines, such as eotaxin, MCP-3, and MCP-4, they can also upregulate the expression of other chemokines, including IL-8, IP-10, and MCP-2. The failure of oral corticosteroids to inhibit IL-8 mRNA expression might contribute to persistent airway neutrophilia observed in patients with moderate-to-severe asthma, despite treatment with corticosteroids.

Administration, Oral↗

PubMed2004

Microbial superantigens induce glucocorticoid receptor beta and steroid resistance in a nasal explant model.

OBJECTIVE: To study the role of superantigen (SAg) in inducing glucocorticoid (GC) receptor beta and steroid resistance in an explant model of nasal tissue. METHODS: Nasal tissue was obtained from inferior turbinates of controls and ragweed (RW)-sensitive patients. Tissue samples were incubated with SAg of staphylococcal enterotoxin B. In addition, tissue samples from RW-sensitive patients were incubated with RW allergen in the presence and absence of both SAg and dexamethasone (DEX). The expression of GC receptor beta was assessed by immunocytochemistry. The expression of interleukin (IL)-2 and IL-4 mRNA was assessed by in situ hybridization. RESULTS: SAg induced an increase in the expression of GC receptor beta in atopic tissue and to a lesser extent in nonatopic tissue. The most significant induction of GC receptor beta was observed in response to SAg and RW in atopic tissue. Stimulation of atopic tissue with RW alone and SAg alone induced IL-4 and IL-2 mRNA, respectively. Incubation of atopic tissue with both SAg and RW induced both IL-2 and IL-4 mRNA. The increase in IL-4 mRNA expression was blunted by the addition of DEX to atopic tissue stimulated with RW alone but not to tissue stimulated by both RW and SAg. CONCLUSION: Our results demonstrate that SAgs induce steroid resistance in atopic nasal explant tissue by up-regulating the expression of GC receptor beta. Furthermore, we have shown that the up-regulation of GC receptor beta is a local event that is associated with the coexpression of IL-2 and IL-4 mRNA.

Ambrosia↗

PubMed2003

Airway remodeling-associated mediators in moderate to severe asthma: effect of steroids on TGF-beta, IL-11, IL-17, and type I and type III collagen expression.

BACKGROUND: Important features of airway remodeling in asthma include the formation of subepithelial fibrosis and increased deposition of types I and III collagen. TGF-beta, IL-11, and IL-17 are profibrotic cytokines involved in the formation of subepithelial fibrosis and are increased in patients with asthma, particularly in those with severe disease. OBJECTIVE: The purpose of this study was to investigate the effect of corticosteroids on the expression of these profibrotic cytokines and on extracellular matrix deposition. METHODS: We used immunocytochemistry to measure the expression of TGF-beta, IL-11, IL-17, and collagen types I and III in the airways of patients with mild asthma (n = 9), patients with moderate-to-severe asthma (n = 10), and control subjects without asthma (n = 6). Baseline bronchial biopsy specimens were obtained in all groups. In addition, repeat biopsies were obtained in the patients with moderate-to-severe asthma after a 2-week course of oral corticosteroids. RESULTS: TGF-beta expression was significantly higher in all groups with asthma, and it did not decrease after treatment with oral corticosteroids. Levels of IL-11 and IL-17 were increased in patients with moderate-to-severe asthma compared with patients with mild asthma and normal controls (P <.05). The expression of these cytokines decreased with oral corticosteroids in the moderate-to-severe group to levels that were comparable to those seen in the patients with mild asthma and in the normal controls (P <.005). Expression of types I and III collagens was higher in the patients with moderate-to-severe asthma than in the patients with mild asthma and the controls (P <.05; P <.001). Treatment with corticosteroids did not decrease the expression of types I and III collagens. CONCLUSIONS: These results confirm the association of increased levels of TGF-beta, IL-11, IL-17, and types I and III collagens with severe disease and suggest that the failure of cortico-steroids to decrease collagen deposition might be due to persistently elevated TGF-beta expression.

Administration, Oral↗