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Interleukin (IL)-13 is a T helper 2-derived cytokine that has recently been implicated in allergic airway responses. We hypothesized that IL-13 may regulate expression of eotaxin in airway epithelium. We found that IL-13 upregulated eotaxin messenger RNA and protein synthesis in the airway epithelial cell line BEAS-2B; this effect showed synergy with tumor necrosis factor (TNF)-alpha and also was inhibited by the glucocorticoid budesonide. To establish the mechanisms of eotaxin upregulation by IL-13, cells were transfected with an eotaxin promoter-luciferase reporter plasmid and transcription was activated by IL-13 (1.7-fold) and TNF-alpha (2.8-fold). The combination of IL-13 and TNF-alpha additively activated the promoter constructs (4.1-fold). Activation of signal transducer and activator of transcription (STAT) 6 by IL-13 was confirmed by nuclear protein binding to a DNA probe derived from the eotaxin promoter. Activation of eotaxin transcription by IL-13 and the additive effect with TNF-alpha were lost in plasmids mutated at a putative STAT6 binding site. Cotransfection with a wild-type STAT6 expression vector significantly enhanced activation of the eotaxin promoter after IL-13 stimulation (6-fold induction). A significant increase of eotaxin protein secretion in the supernatant of STAT6 wild-type-transfected cells was observed after IL-13 stimulation. Cotransfection with a dominant negative STAT6 mutant expression vector inhibited activation of the eotaxin promoter by IL-13. These results indicate that IL-13 stimulates eotaxin expression in airway epithelial cells and that STAT6 plays a pivotal role in this response.

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The chemokine regulated on activation, normal T cells expressed and secreted (RANTES), is a C-C chemokine and a potent chemoattractant for monocytes, T lymphocytes, basophils, and eosinophils. Its expression by human airway epithelium has been demonstrated both in vitro and in vivo. We investigated whether RANTES is expressed by normal human airway epithelial cells after influenza viral infection and examined its bioactivity. Epithelial cells were obtained from bronchial tissue or nasal polyps of patients who had undergone lobectomy for lung cancer or polypectomy for nasal polyps. These cells were cultured by the outgrowth method. Cultured cells were infected with influenza virus A (subtype H3N2) after which the supernatants and the cells were collected 8 to 72 h after infection. RANTES mRNA (messenger RNA) was analyzed by the reverse transcriptase-polymerase chain reaction and Southern blot analysis of its product. Concentrations of RANTES in the supernatants were analyzed by enzyme-linked immunosorbent assay. RANTES protein and mRNA were not detected in the media of uninfected cells. PCR products for RANTES were clearly detected in nasal and bronchial epithelial cells 24 h after infection. Southern blot analysis confirmed that the PCR products were indeed specific for RANTES mRNA. Twenty-four to 72 h after infection, significant levels of RANTES protein were detected in culture media. We also investigated the chemotactic activity of the supernatant of cultured cells. The supernatant of the cells 48 h after infection had potent chemotactic activity for eosinophils, which was attenuated by the addition of anti-RANTES antibodies. These findings suggest that influenza virus infection may induce expression of bioactive RANTES by normal human bronchial and nasal epithelial cells.

TLR3 is expressed inside airway epithelial cells and transduces synthetic dsRNA signals. These signals may increase expression of inflammatory cytokines, chemokines and ICAM-1 through activation of transcription factors NF-kappaB and/or IRF3 in airway epithelial cells.

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2 exhibited abnormal morphology, suggesting a unique functional aspect of this enzyme. Based on the present results as well as our current analyses on the group I/II/V/X sPLA 2 s, general properties of cellular actions of a full set of mammalian sPLA 2 s in regulating AA metabolism are discussed.