The antimicrobial protein short palate, lung, and nasal epithelium clone 1 (SPLUNC1) is differentially modulated in eosinophilic and noneosinophilic chronic.

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The antimicrobial protein short palate, lung, and nasal epithelium clone 1 (SPLUNC1) is differentially modulated in eosinophilic and noneosinophilic chronic rhinosinusitis with nasal polyps Yi Wei, MD, Wentong Xia, MD, Xingling Ye, MD, Yunping Fan, PhD, Jianbo Shi, PhD, Weiping Wen, PhD, Pingchang Yang, PhD, Huabin Li, MD Journal of Allergy and Clinical Immunology Volume 133, Issue 2, Pages 420-428.e12 (February 2014) DOI: 10.1016/j.jaci.2013.09.052 Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 SPLUNC1 mRNA expression in nasal tissues. SPLUNC1 (A), LPLUNC2 (B), BPI (C), TLR2 (D), TLR3 (E), and TLR4 (F) mRNA levels were significantly reduced in polyp tissues from patients with CRSwNP compared with values seen in the other subgroups. Results are expressed as medians (interquartile ranges). *P < .05, **P < .01, and ***P < .001. Journal of Allergy and Clinical Immunology 2014 133, 420-428.e12DOI: (10.1016/j.jaci.2013.09.052) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Protein expression and distribution of SPLUNC1 in nasal tissues. Representative Western blot results (A), densitometric analysis (B), ELISA analysis (C), quantitative analysis of SPLUNC1 staining intensity (D), and representative SPLUNC1 staining (E; ×200 and ×400 magnification) in nasal tissues from patients with CRSwNP and those with CRSsNP, as well as control subjects, is shown. Data are expressed as medians (interquartile ranges). ***P < .001. Journal of Allergy and Clinical Immunology 2014 133, 420-428.e12DOI: (10.1016/j.jaci.2013.09.052) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 SPLUNC1 mRNA and protein expression in eosinophilic (EOS) and noneosinophilic (nEOS) polyp tissues. A, mRNA expression of SPLUNC1 in polyp tissues. B-D, ELISA analysis (Fig 3, B), representative Western blot results (Fig 3, C), and densitometric analysis (Fig 3, D) of SPLUNC1 in tissue extracts of nasal polyps. ***P < .001. Journal of Allergy and Clinical Immunology 2014 133, 420-428.e12DOI: (10.1016/j.jaci.2013.09.052) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 SPLUNC1 mRNA and protein levels in cultured PECs and A549 cells in response to TLR agonists. A, SPLUNC1 mRNA expression after a 12-hour stimulation. B, ELISA analysis of SPLUNC1 levels in supernatants after a 24-hour stimulation. C and D, Representative Western blot results of cell lysates (Fig 4, C) and densitometric analysis (Fig 4, D) after a 24-hour stimulation. Results represent mean values from 3 independent experiments. Data are expressed as means (SEMs). *P < .05, **P < .01, and ***P < .001. PGN, Peptidoglycan; PolyI:C, polyinosinic-polycytidylic acid. Journal of Allergy and Clinical Immunology 2014 133, 420-428.e12DOI: (10.1016/j.jaci.2013.09.052) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 SPLUNC1 mRNA expression in cultured PECs and A549 cells in response to proinflammatory cytokines. A, SPLUNC1 mRNA expression after a 12- or 24-hour stimulation. B-D, Representative Western blot results (Fig 5, B), densitometric analysis (Fig 5, C), and ELISA analysis (Fig 5, D) of SPLUNC1 levels in supernatants after a 24-hour stimulation. Results represent mean values from 3 independent experiments. Data are expressed as means (SEMs). *P < .05, **P < .01, and ***P < .001. Journal of Allergy and Clinical Immunology 2014 133, 420-428.e12DOI: (10.1016/j.jaci.2013.09.052) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Submucosal gland number and staining intensity in nasal tissues. A, Representative results after PAS staining (×200 magnification). B and C, Mean number (Fig E1, B) and glandular staining intensity (Fig E1, C) of submucosal glands. Results are expressed as medians (interquartile ranges). ***P < .001. Journal of Allergy and Clinical Immunology 2014 133, 420-428.e12DOI: (10.1016/j.jaci.2013.09.052) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 SPLUNC1 expression and submucosal glandular staining in tissue from patients with eosinophilic (EOS) and noneosinophilic (nEOS) CRSwNP. A, Representative results of MBP, SPLUNC1, and PAS staining (×200 magnification). B, Number of tissue eosinophils (MBP-positive cells per high-power field [HPF], ×200 magnification). C, SPLUNC1 immunostaining intensity. D and E, Mean number (Fig E2, D) and glandular staining intensity (Fig E2, E) of submucosal glands. Data are expressed as medians (interquartile ranges). ***P < .001. Journal of Allergy and Clinical Immunology 2014 133, 420-428.e12DOI: (10.1016/j.jaci.2013.09.052) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E3 Histologic profiles of tissues from patients with eosinophilic (EOS) and noneosinophilic (nEOS) CRSwNP. A, Representative results of MBP, H&E, and Masson trichrome staining (×200 magnification). B, Semiquantitative score of tissue edema. C, Percentage of area covered by collagen deposition. Data are expressed as medians (interquartile ranges). ***P < .001. Journal of Allergy and Clinical Immunology 2014 133, 420-428.e12DOI: (10.1016/j.jaci.2013.09.052) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E4 Tissue distribution, as well as mRNA and protein expression, of TLR2, TLR3, and TLR4 in tissue from patients with eosinophilic (EOS) and noneosinophilic (nEOS) CRSwNP. A-C, Representative TLR immunostaining in polyp tissues (×200 magnification). D-F, mRNA expression of TLR2,TLR3, and TLR4. G-J, Representative Western blot results (Fig E4, G) and densitometric analysis (Fig E4, H-J) of TLR2, TLR3, and TLR4 protein expression. **P < .01 and ***P < .001. Journal of Allergy and Clinical Immunology 2014 133, 420-428.e12DOI: (10.1016/j.jaci.2013.09.052) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E5 mRNA expression of the proinflammatory cytokines IL-4 (A), IL-13 (B), IL-1α (C), IFN-γ (D), and IL-17A (E) in eosinophilic (EOS) and noneosinophilic (nEOS) polyp tissues. Data are expressed as medians (interquartile ranges). ***P < .001. Journal of Allergy and Clinical Immunology 2014 133, 420-428.e12DOI: (10.1016/j.jaci.2013.09.052) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E6 mRNA expression of SPLUNC1 in PECs in response to glucocorticoid treatment. SPLUNC1 mRNA levels were significantly upregulated after stimulation with glucocorticoid alone (A) or glucocorticoid in combination with the proinflammatory cytokines IL-4, IL-13, IFN-γ, and IL-17A (B-E). Results represent mean values from 3 independent experiments. Data are expressed as means (SEMs). Bud, Budesonide; Dex, dexamethasone; Flu, fluticasone. *P < .05, **P < .01, and ***P < .001. Journal of Allergy and Clinical Immunology 2014 133, 420-428.e12DOI: (10.1016/j.jaci.2013.09.052) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E7 Protein levels of SPLUNC1 in nasal secretions from patients with CRSwNP. Increased SPLUNC1 in nasal secretions (A) and improved total nasal symptom scores (visual analog scale [VAS] score); (B) before and after patients received glucocorticoid treatment. Solid bars represent median values. ***P < .01. Journal of Allergy and Clinical Immunology 2014 133, 420-428.e12DOI: (10.1016/j.jaci.2013.09.052) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions