Cross-talk between TLR3 and TNF-α or IFN-γ Signaling in Induction of CXCL8/IL-8 and CXCL10/IP-10 Expression in Airway Epithelial Cells

CXCL8/IL-8 is a chemoattractant for neutrophils and mast cells, and regulates inflammatory cell recruitment in allergy, infection, and other neutrophil-related diseases. Interferon (IFN) -γ-inducible protein 10 (CXCL10/IP-10) is a chemokine that attracts mononuclear cells, Th1 cells, and natural killer cells. We investigated the levels of CXCL8/IL-8 and CXCL10/IP-10 expression by airway epithelial cells after exposure to the inflammatory cytokines tumor necrosis factor (TNF) -α and IFN-γ, and to poly I:C, a synthetic analog of double-stranded RNA that is a ligand of Toll-like receptor 3 (TLR3). Poly I:C, TNF-α, IFN-γ, and combinations of poly I:C with TNF-α or IFN-γ were used to stimulate the airway epithelial cell line BEAS-2B. Following stimulation, we determined CXCL8/IL-8 and CXCL10/IP-10 mRNA levels by real-time PCR and protein levels by ELISA. Poly I:C treatment upregulated mRNA and protein expression for both CXCL8/IL-8 and CXCL10/IP-10. The addition of TNF-α, but not IFN-γ, to poly I:C further increased the expression of CXCL8/IL-8 mRNA and protein. The addition of either TNF-α or IFN-γ to the poly I:C treatment further increased CXCL10/IP-10 mRNA and protein expression. Cross-talk between TLR3 signaling and inflammatory cytokines regulates the expression of CXCL8/IL-8 and CXCL10/IP-10 in airway epithelial cells. From our results, TNF-α and IFN-γ produce different effects on TLR3 signaling

Anti-IgE therapy for allergic bronchopulmonary aspergillosis

Allergic bronchopulmonary aspergillosis (ABPA) is a severe type of asthma. Some cases are resistant to treatment, even with regular use of antiasthmatic drugs and antifungal agents. The diagnosis of ABPA was made in a 40-year-old patient with ABPA according to the Rosenberg-Patterson criteria. Symptoms were not controlled despite regular use of antiasthmatic drugs, daily systemic steroids, and antifungal agents. Omalizumab, administered in an attempt to stabilize these uncontrolled symptoms, was effective with no adverse events. Our experience suggests omalizumab is a potential candidate drug for controlling steroid-dependent ABPA

Potential Involvement of IL-17F in Asthma

The expression of IL-17F is seen in the airway of asthmatics and its level is correlated with disease severity. Several studies have demonstrated that IL-17F plays a pivotal role in allergic airway inflammation and induces several asthma-related molecules such as CCL20. IL-17F-induced CCL20 may attract Th17 cells into the airway resulting in the recruitment of additional Th17 cells to enhance allergic airway inflammation. We have recently identified, for the first time, that bronchial epithelial cells are its novel cell source in response to IL-33 via ST2-ERK1/2-MSK1 signaling pathway. The receptor for IL-17F is the heterodimeric complex of IL-17RA and IL-17RC, and IL-17F activates many signaling pathways. In a case-control study of 867 unrelated Japanese subjects, a His161 to Arg161 (H161R) substitution in the third exon of the IL-17F gene was associated with asthma. In atopic patients with asthma, prebronchodilator baseline FEV1/FVC values showed a significant association with the H161R variant. Moreover, this variant is a natural antagonist for the wild-type IL-17F. Moreover, IL-17F is involved in airway remodeling and steroid resistance. Hence, IL-17F may play an orchestrating role in the pathogenesis of asthma and may provide a valuable therapeutic target for development of novel strategies

The Risks of Using Personally Imported Traditional Chinese Drugs (Decoction)

金沢大学医薬保健研究域薬学系In Chinese herbal drugs, different drugs have the same name, causing confusion of drug origin which might cause harmful effects when clinically applied. We examined a 19-year-old female who acquired Chinese herbs syndrome (aristolochia nephropathy) induced by a mixture of crude Chinese drugs. She had imported the Chinese drug (decoction) consisting of approximately 20 natural elements and taken it for atopic dermatitis over a course of approximately 3 years. We identified "Guan Mutong" of Aristolochiaceae as analyzed by means of thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC). We confirmed aristolochic acid, a known nephrotoxin, from stem slices of "Guan Mutong" in her drug. It is not known if "Guan Mutong" was intentionally included in her imported Chinese drugs or put in by mistake. However, the present study has suggested the possibility that the Chinese herb "Guan Mutong" which is potentially nephrotoxic, might be accidentally delivered in the plant fraction of the Chinese drug. The possible adverse effects of crude Chinese drugs should be emphasized for patients who self-administer them

Effect of a leukotriene receptor antagonist pranlukast hydrate, on airway inflammation airway hyperresponsiveness in patients with moderate to severe asthma

Asthma is characterized by chronic airway inflammation and the recruitment of inflammatory cells, typically eosinophils and lymphocytes, into the airway. Although several chemical mediators are released during the inflammatory process of asthma, evidence strongly suggests that the cysteinyl leukotrienes (LT), LTC4, LTD4, and LTE4, play key roles in asthma. The short-term clinical efficacy of an LT receptor antagonist, pranlukast hydrate, in symptomatic patients with asthma who had already been treated with moderate to high doses of inhaled corticosteroids was therefore investigated. Treatment with pranlukast hydrate for 4 weeks significantly improved respiratory function and decreased asthma symptoms, the rescue use of inhaled β2-agonists, the number of peripheral blood eosinophils and serum levels of eosinophil cationic protein. Furthermore, airway inflammation, as evaluated by the percentage of eosinophils in induced sputum and airway responsiveness to histamine, decreased significantly after treatment. There were no significant changes in these parameters in control patients with asthma whose treatment was not changed over 4 weeks. These preliminary results suggest that pranlukast hydrate, an LT receptor antagonist, is an effective agent in the management of asthma in combination with moderate to high doses of inhaled corticosteroids