Role of Interleukin-10 on Nasal Polypogenesis in Patients with Chronic Rhinosinusitis with Nasal Polyps

<div><p>Background and Objectives</p><p>Interleukin 10 (IL-10) is a potent anti-inflammatory cytokine. The dysregulation of IL-10 is associated with an enhanced immunopathologic response to infection, as well as with an increased risk for developing numerous autoimmune diseases. In this study, we investigated IL-10 expression in chronic rhinosinusitis with nasal polyps (CRSwNP) and assessed the possible role of IL-10 in the pathogenesis of CRSwNP.</p><p>Materials and Methods</p><p>Thirty-five patients with CRSwNP, 12 patients with chronic rhinosinusitis without NP (CRSsNP) and 10 control subjects were enrolled in this study. NP tissues and uncinated tissues (UT) were collected for analysis. Dispersed NP cells (DNPCs) were cultured in the presence or absence of IL-25 and IL-10, and a flow cytometric assay was performed to identify the constitutive cell populations of the DNPCs. Murine NP (<i>n</i> = 18) models were used for the in vivo experiments. Real-time PCR, immunohistochemistry, western blotting analysis and ELISA were performed to measure the expression levels of the selected inflammatory cytokines and inflammation-associated molecules.</p><p>Results</p><p>The mRNA expression levels of IL-10, IL-5, IL-17A, IL-25 and interferon gamma (IFN-γ) were significantly higher in the NP tissues than in the UT tissues. Strong positive correlations were observed between IL-10 and a variety of inflammatory cytokines (IL-5, IL-17A, IL-25, IFN-γ) and inflammation-associated molecules (B-cell activating factor; BAFF, CD19). Other than the IL-25 to IL-10 ratio, the expression ratios of the other measured inflammatory cytokines to IL-10 were significantly lower in the CRSwNP group than in the CRSsNP or control groups. Administrating IL-25 into the cultured DNPCs significantly increased the production of IL-10, but administrating IL-10 had no effect on the production of IL-25.</p><p>Conclusion</p><p>Increased expression of IL-10, IL-10 related inflammatory cytokine, and IL-10 related B cell activation indicated that IL-10, a potent anti-inflammatory cytokine, has a pivotal role in the pathogenesis of CRSwNPs.</p></div

Expression of T helper and innate cytokines among the groups.

<p>mRNA expression of T helper (IL-4, IL-5, IL-17A, and IFN-γ) and innate (IL-25, and IL-33) cytokines using real time PCR (A to F) among the groups. * = <i>p</i><0.05, ** = <i>p</i><0.01, *** = <i>p</i><0.001.</p

Patient characteristics.

<p>Patient characteristics.</p

Detection of Staphylococcal SpA.

<p>A large amount of Staphylococcus SpA was detected in the NP of CRSwNP compared to the UT of the control group or patients with CRSsNP (Immunofluorescent staining A and B). * = <i>p</i><0.05, ** = <i>p</i><0.01, *** = <i>p</i><0.001.</p

Expression of IL-10 and other cytokines in murine polyp model.

<p>Expressions of IFN-γ (A), IL-5 (B), IL-17A (C), IL-25 (D) and IL-10 (F) were significantly higher in the 3 months and 6 months murine polyp model than in control mice. Expression of IL-33 (E) was significantly lower in the 3 months and 6 months mouse model compared with the control mice. The protein level of IL-10 in the nasal lavage fluid was significantly higher in long-term CRS model groups compared with the control group (G). * = p<0.05, ** = p<0.01, *** = p<0.001.</p

Influence of IL-10 expression on B cell population in the tissue.

<p>Expression of BAFF (A) and CD19 (B) mRNA among the groups. There was significant correlation in mRNA expression between IL-10 and BAFF (C) as well as between IL-10 and CD19 (D). CD19 and BAFF also showed significant correlation in their mRNA expression (E). * = p<0.05, ** = p<0.01, *** = p<0.001, r = Spearman’s rank correlation coefficient.</p

Expression of IL-10 among the different groups.

<p>A, mRNA expression of IL-10 in the UT tissue or NP tissue among groups. B, representative images of western blot assay and relative expression of IL-10 in the UT or NP among the groups. C, representative images of IL-10 immunohistochemistry and the number of IL-10 positive cells in the tissues from the different groups. CRSsNP, chronic rhinosinusitis without NP; CRSwNP, chronic rhinosinusitis with NP. * = <i>p</i><0.05, ** = <i>p</i><0.01, *** = <i>p</i><0.001.</p

Double immunofluorescent staining of IL-10 and IL-25 in NP.

<p>Some of the cells in the subepithelial space of NP from patients with CRSwNP produced both IL-10 and IL-25 at the same time (A, white arrow). The number of double positive cells (IL-25⁺ IL-10⁺ cells) was considerably higher in the NP tissues of the CRSwNP group compared to the other groups and also much higher in the UT of the CRSwNP compared to the UT of the control group (B). ** = <i>p</i><0.01, *** = <i>p</i><0.001, **** = <i>p</i><0.0001.</p

Correlations between IL-10 and inflammatory cytokine expressions in tissues from patients.

<p>Expression of IL-10 showed significant positive correlation with IL-5 (B), IFN-γ (C), IL-17A (D) and IL-25 (E) expressions in all patients. Expression of IL-10 and IL-33 showed significant negative correlation in all patients (F). There was no significant correlation between IL-10 and IL-4 (A). <i>r</i> = <i>Spearman</i>’s rank correlation coefficient.</p

Soft Template-Assisted Fabrication of Mesoporous Graphenes for High-Performance Energy Storage Systems

Graphene is a promising active material for electric double layer supercapacitors (EDLCs) due to its high electric conductivity and lightweight nature. However, for practical uses as a power source of electronic devices, a porous structure is advantageous to maximize specific energy density. Here, we propose a facile fabrication approach of mesoporous graphene (m-G), in which self-assembled mesoporous structures of poly(styrene)-block-poly(2-vinylpyridine) copolymer (PS-b-P2VP) are exploited as both mesostructured catalytic template and a carbon source. Notably, the mesostructured catalytic template is sufficient to act as a rigid support without structural collapse, while PS-b-P2VP converts to graphene, generating m-G with a pore diameter of ca. 3.5 nm and high specific surface area of 186 m2/g. When the EDLCs were prepared using the obtained m-G and ionic liquids, excellent electrochemical behaviors were achieved even at high operation voltages (0 ∼ 3.5 V), including a large specific capacitance (130.2 F/g at 0.2 A/g), high-energy density of 55.4 W h/kg at power density of 350 W/kg, and excellent cycle stability (>10,000 cycles). This study demonstrates that m-G is a promising material for high-performance energy storage devices