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¹ßÇ¥Çü½Ä : Á¢¼ö¹øÈ£ - 980275    RHOP 3-4 
NEUTROPHIL-PRODUCING CYTOKINES IN THE ENDOTYPES OF CHRONIC RHINOSINUSITIS WITH NASAL POLYPS
DEPARTMENT OF OTORHINOLARYNGOLOGY-HEAD & NECK SURGERY, BORAMAE MEDICAL CENTER, SEOUL NATIONAL UNIVERSITY COLLEGE OF MEDICINE, SEOUL, SOUTH KOREA
ARA JO, DAE WOO KIM
¸ñÀû: Chronic rhinosinusitis with nasal polyps (CRSwNP) includes very diverse inflammatory cells, which are thought to play an important role in CRSwNP pathophysiology. However, neutrophils remain elusive cells in CRSwNP. This study was performed to investigate the functional changes of neutrophils in response to inflammatory stimuli. ¹æ¹ý:Bloods and nasal tissues were collected from patients with CRSwNP and control subjects. Type 2 and non-type 2 CRSwNP were classified based on blood counts of eosinophils (greater or lesser than 250 cells/¥ìL). Tissue neutrophils (TN) and blood neutrophils (BN) were stimulated with lipopolysaccharide (LPS) and IL-4. After the stimulation, the supernatants were collected and the protein levels of various inflammatory cytokines and several typical N1 (CCL3, CXCL9, CXCL10, Fas/CD95) and N2 (CCL2, CCL5, MMP9, VEGF) markers were measured using multiplex immunoassays. °á°ú:The expression levels of N1-related proteins (CCL3, CXCL9, and Fas/CD95) were and N2-related proteins (CCL2, MMP9, and VEGF) were also all significantly higher in LPS-treated BN, regardless of endotype. In LPS-treated TN of type 2 and non-type 2 CRSwNP, the N1 marker Fas/CD95 and N2 marker CCL2 were significantly decreased. However, another N1 marker CXCL9 was significantly decreased, especially in type 2 CRSwNP. Inflammatory cytokine levels (IL-1¥â, IL- 6, IL-8/CXCL8, IL-17A, IL-23, IL-33 and TNF-¥á) were found to be significantly higher in LPS-treated BN, regardless of endotype. IL-10 was significantly increased in control and type2 CRSwNP. Consistent with LPS-treated BN, TNF-¥á, IL-6 and IL-8/CXCL8 were significantly increased in TN. In LPS-treated TN of type 2 and non-type 2 CRSwNP, the IL-17A was significantly decreased and TGF-¥â was significantly increased. IL-10 and IL-12p70 were significantly decreased in LPS- treated TN of type 2 CRSwNP. In addition, N2 markers (CCL2 and CCL5) were significantly increased and IL-13 and IFN¥ã were all significantly decreased in IL-4-treated BN regardless of endotype. N2 marker (MMP9), IL-17A and IL-18 were significantly decreased in IL-4- treated BN of type 2 CRSwNP. IL-4-treated TN showed higher expression levels of the CCL5 (N2) in type 2 and non-type 2 CRSwNP. IL-33 was significantly increased in IL-4-treated TN of type 2 CRSwNP. °á·Ð:This study indicate that neutrophils perform various functional roles based on their location and stimuli, exhibiting diminished protective functions in type 2 inflammatory conditions.


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