Inhaled delivery of recombinant interferon-lambda restores allergic inflammation after development of asthma by controlling Th2- and Th17-cell-mediated immune responses.

Remarkable progress has recently been achieved to identify the biological function and potential value of novel therapeutic targets for the effective control of allergic asthma. Interferon (IFN)-λ has been suggested to restrict chronic inflammation in the lungs of asthmatic mice and we sought to determine the contribution of IFN-λ as an asthma therapeutic. We show that inhaled IFN-λ can restrict Th2 and Th17 inflammation in the lungs of asthmatic mice, accompanied with alteration of IL-10 secretion. BALB/C mice were used for an asthmatic mouse model with OVA. Recombinant IFN-λs (IFN-λ2: 2 µg, IFN-λ3: 2 µg) were inoculated into asthmatic mice after OVA challenge by intranasal delivery. Lungs of asthmatic mice were severely inflamed, with extensive inflammatory cell infiltration and increased goblet cell metaplasia with higher total lung resistance. Transcription of IL-4, IL-5, IL-13, and IL-17A was significantly higher until five days after the final OVA challenge. Asthmatic mice were administered recombinant IFN-λ via inhalation three times after the last challenge and the asthmatic mice showed improvement in lung histopathologic findings, and total lung resistance was maintained under normal range. IFN-λ inhalation exhibited significant decreases in Th2 and Th17 cytokine levels, and the populations of Th2 and Th17 cells were recovered from the lungs of asthmatic mice. Additionally, increase in IL-10 secretion from CD4 + Th cells population was observed in response to inhaled delivery of IFN-λ along with alterations in Th2 and Th17 cell-derived inflammation. Our findings show that inhaled delivery of IFN-λ can restrict airway inflammation in the lungs of asthmatic mice by controlling Th2- and Th17-mediated responses accompanied by regulation of IL-10 secretion even after asthma development.

Expression and regulation of PLUNC in human nasal epithelium.

CONCLUSIONS: We demonstrated that PLUNC (palate, lung, and nasal epithelium clone) is secreted from nasal epithelial cells and is not influenced by differentiation or proinflammatory mediators. The functional role of PLUNC in the human airway has yet to be elucidated. OBJECTIVES: The localization and regulation of PLUNC protein in human nasal epithelium was investigated. First, we located epithelial cells expressing PLUNC protein in human nasal mucosa. Secondly, we sought to identify PLUNC protein in either human nasal secretions from healthy volunteers or apical secretions from cultured human nasal epithelial cells. Lastly, we investigated whether epithelial differentiation and proinflammatory cytokines influence the expression of PLUNC in human nasal epithelial cells. MATERIALS AND METHODS: Immunohistochemical staining for PLUNC was conducted on nasal turbinate specimens. Western blot analysis was conducted on nasal secretions from healthy volunteers, apical secretion from cultured human nasal epithelium, and on normal-appearing posterior ethmoid mucosa, inferior turbinate, and nasal polyp specimens. Reverse transcription-PCR (RT-PCR) of PLUNC was performed with mRNA from cultured human nasal epithelium cells treated with either interleukin-1beta or tumor necrosis factor-alpha. RESULTS: PLUNC was expressed in ciliated cells of surface epithelium and serous cells of the submucosal gland in the human nasal mucosa, and was also found in the nasal secretions of healthy volunteers and apical secretions of cultured human nasal epithelial cells. The degree of mucociliary differentiation and proinflammatory mediators did not influence the expression of PLUNC gene and protein in nasal epithelium.

Effects of prostagladin E(2) on gel-forming mucin secretion in normal human nasal epithelial cells.

CONCLUSION: The findings of this study indicate that prostaglandin E(2) (PGE(2)) induces MUC5AC gene expression and mucin secretion via the EP4 receptor in cultured normal human nasal epithelial cells. OBJECTIVES: Recently, PGE(2) was found to induce MUC5AC production via an agonist of EP2/EP4, but not EP1/EP3, in normal human airway epithelium. However, the receptor that mediates MUC5AC has not been determined. This study aimed to investigate the MUC5AC mucin gene and mucin secretion by PGE(2) and its receptors in cultured normal human nasal epithelial cells. METHODS: After treatment with PGE(2) and/or PGE(2) antagonist, gel-forming mucin mRNA expression was determined by reverse transcription-polymerase chain reaction. Total mucin and MUC5AC mucin levels were measured using an immuno-dot blotting assay. RESULTS: PGE(2) increased only MUC5AC gene expression and MUC5AC mucin, but not expression of other gel-forming mucin genes. An EP2 receptor antagonist (AH 6809) did not suppress the PGE(2)-induced MUC5AC gene expression or MUC5AC mucin. However, an EP4 receptor antagonist (AH23848) significantly suppressed the level of PGE(2)-induced MUC5AC gene expression and MUC5AC mucin.