Publications (2)6.25 Total impact
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Article: Contribution of the proinflammatory cytokine IL-18 in the formation of human nasal polyps.
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ABSTRACT: Nasal polyposis is a chronic inflammatory disease of the nasal mucosa. The etiology and the mechanisms of formation of nasal polyps are still not clear. Interleukin (IL)-18 is a novel proinflammatory cytokine that plays important roles in regulating immune inflammatory responses. However, the presence of IL-18 in human nasal mucosa and its roles in the inflammatory process of nasal polyps has not been studied yet. In this study, it was the first time to investigate the expression of IL-18 in human nasal mucosa and nasal polyps, and its potential function in the formation of nasal polyps. Surgical samples were analyzed by Western blot and immunohistochemistry to evaluate the expression and location of IL-18, and its correlated cytokines, IL-4, and IFN-γ. Furthermore, the airway epithelial cell line, A549, was used to investigate the mutual regulation of IFN-γ, IL-4, and IL-18. IFN-γ, IL-4, and IL-18 were all highly expressed in the epithelial cells, submucosal glands, and infiltrating inflammatory cells in the nasal polyp tissues, comparing with the control samples. Especially, the expression of IL-18 was upregulated significantly in nasal polyp tissues compared with control tissues. In addition, IL-18 was expressed in A549 cells in response to lipopolysaccharide and IL-4. Our data suggest that nasal epithelial cells are involved in the pathogenesis of nasal polyps formation and potentially via the secretion of IL-18, which is likely to play important roles in the formation of nasal polyps.The Anatomical Record Advances in Integrative Anatomy and Evolutionary Biology 06/2011; 294(6):953-60. · 1.47 Impact Factor -
Article: PTB-associated splicing factor (PSF) functions as a repressor of STAT6-mediated Ig epsilon gene transcription by recruitment of HDAC1.
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ABSTRACT: Regulation of transcription requires cooperation between sequence-specific transcription factors and numerous coregulatory proteins. In IL-4/IL-13 signaling several coactivators for STAT6 have been identified, but the molecular mechanisms of STAT6-mediated gene transcription are still not fully understood. Here we identified by proteomic approach that the PTB-associated splicing factor (PSF) interacts with STAT6. In intact cells the interaction was observed only after IL-4 stimulation. The IL-4-induced tyrosine phosphorylation of both STAT6 and PSF is a prerequisite for the efficient association of the two proteins. Functional analysis demonstrated that ectopic expression of PSF resulted in inhibition of STAT6-mediated transcriptional activation and mRNA expression of the Igε germline heavy chain gene, whereas knockdown of PSF increased the STAT6-mediated responses. PSF recruited histone deacetylase 1 (HDAC1) to the STAT6 transcription complex, which resulted in reduction of H3 acetylation at the promoter regions of Ig heavy chain germline Igε and inhibition of STAT6-mediated transcription. In addition, the HDACs inhibitor trichostatin A (TSA) enhanced H3 acetylation, and reverted the PSF-mediated transcriptional repression of Igε gene transcription. In summary, these results identify PSF as a repressor of STAT6-mediated transcription that functions through recruitment of HDAC to the STAT6 transcription complex, and delineates a novel regulatory mechanism of IL-4 signaling that may have implications in the pathogenesis of allergic diseases and pharmacological HDAC inhibition in lymphomas.Journal of Biological Chemistry 02/2011; 286(5):3451-9. · 4.77 Impact Factor
