Qianying Sun

Peking University Health Science Center, Peping, Beijing, China

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Publications (4)12.11 Total impact

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    ABSTRACT: PC3-secreted microprotein (PSMP) or microseminoprotein is a newly discovered secreted protein whose function is currently unknown. In this study, PSMP was found to possess chemotactic ability toward monocytes and lymphocytes, and its functional receptor was identified as CCR2B. PSMP was identified as a chemoattractant protein from a PBMC chemoattractant platform screen that we established. The mature secreted PSMP was able to chemoattract human peripheral blood monocytes, PBLs, and CCR2B-expressing THP-1 cells, but not peripheral blood neutrophils, even though it does not contain the classical structure of chemokines. CCR2B was identified as one receptor for PSMP-mediated chemotaxis by screening HEK293 cells that transiently expressed classical chemokine receptors; results obtained from the chemotaxis, calcium flux, receptor internalization, and radioligand-binding assays all confirmed this finding. To further identify the major function of PSMP, we analyzed its expression profile in tissues. PSMP is highly expressed in benign prostatic hyperplasia and in some prostate cancers, and can also be detected in breast tumor tissue. In response to PSMP stimulation, phosphorylated ERK levels downstream of CCR2B signaling were upregulated in the PC3 cell line. Taken together, our data collectively suggest that PSMP is a chemoattractant protein acting as a novel CCR2 ligand that may influence inflammation and cancer development.
    The Journal of Immunology 01/2014; · 5.36 Impact Factor
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    ABSTRACT: Background: CCR4 is highly expressed on Th2 cells. These cells play an important role in acute inflammatory responses, including those involved in allergic rhinitis. We determined whether disrupting the CCR4 ligand interaction with CCR4 antagonist could alleviate allergic rhinitis in a mouse model. Methods: BALB/c mice were sensitized with ovalbumin and alum by intraperitoneal injection and challenged with intranasally administered ovalbumin. Compound 22, which has been reported as a novel small-molecule antagonist of CCR4, was also administered intranasally. In addition, budesonide, an efficient glucocorticoid, was used as a positive control. The effects of compound 22 were quantified by multiple parameters of allergic responses in both nasal and pulmonary tissues. Results: Compound 22 significantly improved symptoms of allergic rhinitis and suppressed levels of total IgE of serum. It dramatically reduced the levels of IL-4 in bronchoalveolar lavage fluid and also decreased the number of inflammatory cells in the fluid. The infiltration of inflammatory cells, especially eosinophils, was markedly reduced in the nasal and pulmonary tissues. The number of IL-4+ cells was also significantly reduced in these tissues. Moreover, the numbers of Foxp3+ cells and IL-17+ cells were reduced, though not to a statistically significant degree. Conclusions: In our research, CCR4 antagonists such as compound 22 were proven for the first time to alleviate murine allergic rhinitis when administered nasally. CCR4 antagonists may have therapeutic potential for the treatment of allergic rhinitis.
    International Archives of Allergy and Immunology 06/2012; 159(3):297-305. · 2.25 Impact Factor
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    ABSTRACT: Human chemokine-like factor (CKLF1) is a human cytokine that exhibits chemotactic activities on a wide spectrum of leukocytes. One of CKLF1's C-terminal peptides, C19, exerts inhibitory effects on chemotaxis mediated by mouse Ccr3 and Ccr4 and human CCR3 and CCR4. Mouse models of asthma show that C19 can also inhibit the Th2 response. CCR3 and CCR4 are chemokine receptors important to allergic rhinitis, a condition whose pathogenesis is similar to that of asthma. Here, we established a mouse model of allergic rhinitis by repetitive sensitization and intranasal challenge with OVA and assessed whether C19 has therapeutic effects on this model. In this study, both intranasal and intraperitoneal administration of C19 reduced allergic symptoms such as sneezing and rubbing and serum concentration of IgE. C19 showed a strong ability to suppress eosinophil accumulation in nasal mucosa and lung tissues. C19 was able to suppress the Th2 cytokine IL-4 without augmenting the Th1 cytokine IFN-γ in BAL and IL-4(+) cells in the local nasal tissue. In terms of symptom amelioration, IgE reduction, and eosinophilia suppression, C19 was found to be as effective against allergic rhinitis as Budesonide. Moreover, intranasal treatment has a stronger therapeutic effect than other types of administration, and it may be more convenient and safe. For these reasons, C19 may have potential in the treatment of allergic rhinitis.
    International immunopharmacology 12/2011; 11(12):2188-93. · 2.21 Impact Factor
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    ABSTRACT: CKLF1, a human cytokine that is a functional ligand for CCR4, is upregulated in various inflammation and autoimmune diseases. CKLF1 contains at least two secreted forms, the C-terminal peptides C19 and C27. Chemically synthesized C19 and C27 can interact with CCR4 and attenuate allergic inflammation. In this study, we found C19 and C27 could inhibit SDF-1-induced CXCR4-mediated chemotaxis and promote CXCR4 internalization. The inhibitory effect was due to desensitization of CXCR4, which was mediated by CCR4. Further experiments confirmed that CXCR4 desensitization required activation of PI3K/PKC pathway. Altogether our data elucidate the mechanism of C19- and C27-induced CXCR4 desensitization.
    Biochemical and Biophysical Research Communications 06/2011; 409(2):356-61. · 2.28 Impact Factor