The Expression Profile Of Immune-associated Genes In Nasal Polyps

Nasal polyposis (NP) is a chronic mucosal inflammation of the upper airway and often occurs with concurrent chronic rhinosinusitis(CRS).The histology of NP is characterized by the inflammatory cell infiltration (eg, eosinophils, lymphocytes, and plasma cells), structural modifications of epithelium (eg, goblet cell hyperplasia), and lamina propria (LP; eg, extracellular matrix protein accumulation, edema, glandular hyperplasia, and basement membrane thickening). Although a plenty of research has been made on multiple levels, its pathogenesis is still unknown.The pathogenesis of NP not only involved in multiple resident cells and effective cells(epithelial cells, lymphocytes, plasm cells, eosinophils and fibroblast cells), but also involved in different molecules expressed by these cells.These inflammatory cells produced and released vast inflammatory mediators which formed a comprehensive cytokine network. The pro-inflammatory molecules included TNF-α(tumor necrosis factor-α,),IL-4,IL-5,IL-6,IL-8 and GM-CSF (granulocyte-macrophage colony-stimulating factor) ; The chemokines also were procuced, such as RANTES (regulated on activation normal T cell expressed and secreted) and Eotaxin。IL-5, GM-CSF, RANTES and eotaxin contribute to eosinophil migration and survival. Increased levels of IL-8 can induce neutrophil infiltration. Increased expression of vascular endothelial growth factor and its upregulation by transforming growth factor-beta (TGF-β) can contribute to the edema and increased angiogenesis in nasal polyps. Moreover TGF-βcan modulate fibroblast function and thus contribute to eosinophil infiltration and stromal fibrosis. Other mediators like albumin, histamine and immunoglobulins IgE and IgG are also increased in nasal polyps. In addition, the local production of IgE in nasal polyps can contribute to the increased recurrence of nasal polyps via the IgE-mast cell-FcepsilonRI cascade. Finally, mast cell/T cell-epithelial cell/fibroblast interactions can contribute to the persistent eosinophilic inflammation seen in polyps. A recent study detected stayphylococcal superantigen-specific IgE antibodies to the superantigen SEA and SEB in nasal polyp tissue. We explored gene chip technology and got the expression profile of immune associated genes in nasal polyps in order to investigate the expression of these genes including all kinds of cytokines on the whole. Of the 491 immune-associated genes analyzed by microarray, 87 differentially expressed genes were identified. Genes showing altered expression included mainly cytokines and their receptors, chemokines and their receptors, adhesion molecules, leukocyte differential antigen, immune signal transduction molecules. Altered expression also was observed for complements and their receptors, immune transcription regulatory molecules, innate immune and neural immune molecules. 15 genesshowed concomitant different expression involving in monocyte chemotactic protein-2 (MCP-2), intercellular adhesion molecules-3 (ICAM-3), IL-17 receptor, S100 calcium binding protein A2, RAB36, hemofiltrate C-C chemokine-1 (HCC-1), decay accelerating factor for complements (DAF), IgG Fc binding protein and so on. The infiltration of inflammatory cells is the result of the interaction between cells and cells, or between cells and molecules.The migration, activation and self-perpetuation of eosinophils are mediated by many chemokines, adhesion molecules and cytokines. It is the diversity of chemokine receptor expression and the selective release of chemokines that provide a mechanism for the recruitment of different leukocyte populations to inflammatory site. Eosinophils response evoked by eotaxin, RANTES, MCP-2, MCP-3, MCP-4 was mediated through a chemokine receptor, CCR3. MCP-2 and MCP-4 may participate in eosinophils chemotaxis due to the upregulation in the expression profile in nasal polyps. Other upregulated genes such as granulocyte chemotactic protein-2 (GCP-2), γ-interferon induced protein (IP10), ICAM-1, ICAM-3 and CD11c may be chemotactic and adhesive to eosinophils, neutrophils, dentritic cells and thus participate in the inflammatory response in nasal polyp. Tissue remodeling in nasal polyp tissues includes sub-basement membrane deposition of collagen, stromal deposition of extracellular matrix protein, and hypertrophy or hyperplasia of small vascular smooth muscle cells. Platelet-derived growth factor (PDGF) could play a key role in all involved mediators in the remodeling. Eosinophils were likely the potential source of PDGF,and almost all resident eosinophils in nasal polyps and bronchial tissues from severe asthmatic expressed PDGFB [13]. The expression of PDGFC was upregulated in the expression profile. Further research will be needed to elucidate the expression and role of PDGFC in nasal polyps, the relation with PDGFB and the mechanism in its expression in eosinophils. In the expression profile, we still found some innate immune genes and immune signal transduction genes express differently such as Toll-like receptor 3(TLR3), IgG Fc binding protein, S100 calcium binding protein A2, signal transducers and activators of transcription-2(STAT2), tyrosine kinase-2(TYK-2) and so on. The role of innate immunity has been emphasized more and more. Researches about TLR and signal pathway, the mechanism of inducing nonspecific inflammation will provide new approach for the therapy of nasal polyps. The profile results also suggested that IL-17 could play an important role in the pathogenesis of NP, which have been rarely referred in previous research. IL-17 can induce different cells and then produce vast proinflammatory cytokines, which include IL-1β,IL-8 ,iNOS (inducible nitric oxide synthase), COX-2( cyclooxigenase-2 ) and ICAM-1.Furthermore IL-17 can induce haematopoietic cytokines, such as GM-SCF,LIF (Leukemia inhibitory factor),IL-6,which have a close relation with NP. IL-17 connected with IL-17 receptor (IL-17R) with participation of tumor necrosis factor receptor-associated factor 6 (TNAF6), activated nuclear factor κB (NFκB) and activation protein-1 (AP-1) and further...