Seasonal allergic rhinitis caused by Japanese cedar pollen (SAR-JC) is one of the most common allergic diseases in Japan. To identify the genes that related to SAR-JC, we collected nasal samples by brushing inferior turbinate before and during pollen season in 2009. RNA profiles of the samples were analyzed by microarray analysis with Illumina 500GX (Illumina) Subjects were SAR-JC patients (SAR group) and controls without any allergic symptoms/environmental allergens specific IgE (Control group).
We defined over four times fold change between SAR-JC group and Control group as a significant. Eighteen genes were found to be significantly up-regulated after the exposure of allergen. The expression Intelectin 1 exhibited 17.4 times in SAR-JC group compared to Control group. Real-time reverse transcription-polymerase chain reaction (RT-PCR) verified the same result. We also got the same result in 2010 samples from SAR-JC group. Immunohistochemical staining of inferior turbinate showed that Intelectin1 was expressed in nasal epithelial mucous cells from patient with perennial allergic rhinitis. The stimulation of IL-4 and IL-13 induced Intelectin 1 expression by human cultured nasal epithelial cells. These results indicated that Intelectin 1 might be the candidate gene related to onset of allergic rhinitis.

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Nasal natural killer (NK)/T-cell lymphoma is an Epstein-Barr virus (EBV)-related malignancy with poor prognosis and has distinct histological features characterized by angiocentric and polymorphous lymphoreticular infiltrates including inflammatory cells such as granulocytes, monocytes, macrophages and lymphocytes. Recently, the role of chemokines in tumor proliferation and invasion has been shown. Furthermore, chemokines are likely to play important roles in the pathophysiology of diseases associated with EBV. We examined the chemokines expressed by nasal NK/T-cell lymphoma. Nasal NK/T-cell lymphoma cell lines produced IP-10, TARC, MDC, IL-8, and MCP-1. IP-10 enhanced lymphoma cell invasion through an autocrine mechanism. Next, we examined whether inflammatory cells influence the biological activities of nasal NK/T-cell lymphoma cell lines. We cocultured nasal NK/T-cell lymphoma cell lines with monocytes. Cocultured monocytes enhanced the proliferation of cell lines. Immunohistological studies showed confirmation that a number of infiltrating CD14-positive monocytes were in contact with CD56-positive lymphoma cells in the nasal NK/T-cell lymphoma tissues. These results suggest that chemokines such as IP-10, MDC, and MCP-1 produced by nasal NK/T-cell lymphoma cells attract monocytes through a paracrine mechanism and the attracted monocytes enhance proliferation of lymphoma cells.

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In seasonal allergy (such as Japanese cedar pollinosis), pollen specific IgE Ab production has been persistent even in the absent season of allergens. Since long-lived plasma cells (LL-PCs) in bone marrow (BM) are important for the maintenance of serum Ab titers, the persistent production of IgE Abs in Allergic patients may be due to IgE-LL-PCs in BM. However, IgE-LL-PCs in murine BMs have never been detected. Moreover, high concentration of IgE Abs was detected in serum of nasal polyposis patients and IgE-PCs were accumulated in the nasal polyposis tissue.
In this study, we investigated the mechanism of IgE-LL-PCs generation using IL-21R-KO mice which have high concentration of serum IgE titers. When the number of IgE-PCs was examined in IL-21R-KO mice by ELISPOT assay, no IgE-PCs were detected in BM, despite of the high serum IgE concentration. Then, we have established the culture system to generate LL-PCs from naive B cells using IL-21, and those IgE-PCs were transferred into mice to examine the generation of IgE-LL-PCs in BMs.
Since LL-PCs are derived from germinal center (GC) B cells was impaired in IL-21R-KO mice, we will discuss the role of IL-21 in the generation of LL-PCs including IgE-LL-PCs.
These results suggested that IgE-LL-PCs would provide a new target for immunotherapy in Allergic diseases.

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Heparin is a member of a family of polyanionic polysaccharides called glycosaminoglycans, and is one of the most important anticoagulant drugs. Heparin also has a variety of anti-inflammatory functions, and is clinically used as an anti-inflammatory drug. In the lower airways, it has been reported that heparin attenuated eosinophil infiltration and Muc5ac mRNA expression in rat model of asthma, and inhaled heparin is effective for the treatment of patients with asthma. However, little is known about the regulatory effects of heparin on the upper airway inflammation.
We have examined the in vivo and in vitro effects of heparin on mucus hypersecretion in airway epithelial cells. Intranasal instillation with low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) significantly inhibited lipopolysaccharides (LPS)-induced and antigen-induced mucus hypersecretion in rat nasal epithelium. Mucosal infiltration of neutrophils and eosinophils were also significantly attenuated. The in vitro effects of heparin on secretion of mucin and cytokines were examined using cultured airway epithelial cells (NCI-H292). LMWH and UFH significantly inhibited TNF-α-induced secretion of mucin (MUC5AC) and IL-8. These results indicated that local administration with heparin may provide a new therapeutic strategy for upper airway inflammation.

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