Evidence for altered activity of the IL-6 pathway in chronic rhinosinusitis with nasal polyps

Anju T. Peters, Atsushi Kato, Ning Zhang, David B. Conley, Lydia Suh, Brian Tancowny, Derek Carter, Tara Carr, Michael Radtke, Kathryn E. Hulse, Sudarshan Seshadri, Rakesh Chandra, Leslie C. Grammer, Kathleen E. Harris, Robert Kern, Robert P. Schleimer*

*Corresponding author for this work

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

Background: IL-6 activates TH17 cells and regulates the response of B lymphocytes and regulatory T cells. The IL-6 receptor and the membrane protein, glycoprotein 130 (gp130), form an active signaling complex that signals through signal transducer and activator of transcription 3 (STAT3) and other signaling molecules. Both the IL-6 receptor (IL-6R) and gp130 can be found in soluble forms that regulate the pathway. Objective: We measured IL-6 signaling components and IL-17 in chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), CRS without nasal polyps (CRSsNP), and controls to assess the IL-6 pathway in CRS. Methods: IL-6, soluble IL-6R, soluble gp130 (sgp130), and IL-17 were measured in sinus tissue extracts and in nasal lavage fluid by either cytokine bead array or ELISA. phosphoSTAT3 (p-STAT3) was determined by Western blot and by immunohistochemistry. Results: IL-6 protein was significantly (P < .001) increased in CRSwNP compared with CRSsNP and controls. Soluble IL-6R was also increased in nasal polyp compared with control tissue (P < .01). Despite elevated IL-6 and sIL-6R, IL-17A, E, and F were undetectable in the sinus tissue from most of the patients with CRS and controls. p-STAT3 levels were reduced in the polyp tissue, possibly indicating reduced activity of IL-6 in the tissue. sgp130 was elevated in CRSwNP compared with CRSsNP and controls. Conclusion: p-STAT3 levels are decreased in CRSwNP despite increased levels of IL-6 and sIL-6R and are associated with the absence of an IL-17 response. This may be a response to elevated levels of sgp130, a known inhibitor of IL-6 signaling. These results indicate that IL-6 and its signaling pathway may be altered in CRSwNP.

Original languageEnglish (US)
JournalJournal of Allergy and Clinical Immunology
Volume125
Issue number2
DOIs
StatePublished - Jan 1 2010

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Nasal Polyps
Interleukin-6
Interleukin-6 Receptors
STAT3 Transcription Factor
Interleukin-17
Cytokine Receptor gp130
Nasal Lavage Fluid
Th17 Cells
Tissue Extracts
Membrane Glycoproteins
Regulatory T-Lymphocytes
Polyps
Glycoproteins
Membrane Proteins
B-Lymphocytes
Western Blotting
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry
Cytokines

Keywords

  • Chronic rhinosinusitis
  • IL-17
  • IL-6
  • IL-6 receptor
  • nasal polyps
  • phospho-STAT3
  • soluble glycoprotein 130

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Peters, Anju T. ; Kato, Atsushi ; Zhang, Ning ; Conley, David B. ; Suh, Lydia ; Tancowny, Brian ; Carter, Derek ; Carr, Tara ; Radtke, Michael ; Hulse, Kathryn E. ; Seshadri, Sudarshan ; Chandra, Rakesh ; Grammer, Leslie C. ; Harris, Kathleen E. ; Kern, Robert ; Schleimer, Robert P. / Evidence for altered activity of the IL-6 pathway in chronic rhinosinusitis with nasal polyps. In: Journal of Allergy and Clinical Immunology. 2010 ; Vol. 125, No. 2.
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title = "Evidence for altered activity of the IL-6 pathway in chronic rhinosinusitis with nasal polyps",
abstract = "Background: IL-6 activates TH17 cells and regulates the response of B lymphocytes and regulatory T cells. The IL-6 receptor and the membrane protein, glycoprotein 130 (gp130), form an active signaling complex that signals through signal transducer and activator of transcription 3 (STAT3) and other signaling molecules. Both the IL-6 receptor (IL-6R) and gp130 can be found in soluble forms that regulate the pathway. Objective: We measured IL-6 signaling components and IL-17 in chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), CRS without nasal polyps (CRSsNP), and controls to assess the IL-6 pathway in CRS. Methods: IL-6, soluble IL-6R, soluble gp130 (sgp130), and IL-17 were measured in sinus tissue extracts and in nasal lavage fluid by either cytokine bead array or ELISA. phosphoSTAT3 (p-STAT3) was determined by Western blot and by immunohistochemistry. Results: IL-6 protein was significantly (P < .001) increased in CRSwNP compared with CRSsNP and controls. Soluble IL-6R was also increased in nasal polyp compared with control tissue (P < .01). Despite elevated IL-6 and sIL-6R, IL-17A, E, and F were undetectable in the sinus tissue from most of the patients with CRS and controls. p-STAT3 levels were reduced in the polyp tissue, possibly indicating reduced activity of IL-6 in the tissue. sgp130 was elevated in CRSwNP compared with CRSsNP and controls. Conclusion: p-STAT3 levels are decreased in CRSwNP despite increased levels of IL-6 and sIL-6R and are associated with the absence of an IL-17 response. This may be a response to elevated levels of sgp130, a known inhibitor of IL-6 signaling. These results indicate that IL-6 and its signaling pathway may be altered in CRSwNP.",
keywords = "Chronic rhinosinusitis, IL-17, IL-6, IL-6 receptor, nasal polyps, phospho-STAT3, soluble glycoprotein 130",
author = "Peters, {Anju T.} and Atsushi Kato and Ning Zhang and Conley, {David B.} and Lydia Suh and Brian Tancowny and Derek Carter and Tara Carr and Michael Radtke and Hulse, {Kathryn E.} and Sudarshan Seshadri and Rakesh Chandra and Grammer, {Leslie C.} and Harris, {Kathleen E.} and Robert Kern and Schleimer, {Robert P.}",
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Evidence for altered activity of the IL-6 pathway in chronic rhinosinusitis with nasal polyps. / Peters, Anju T.; Kato, Atsushi; Zhang, Ning; Conley, David B.; Suh, Lydia; Tancowny, Brian; Carter, Derek; Carr, Tara; Radtke, Michael; Hulse, Kathryn E.; Seshadri, Sudarshan; Chandra, Rakesh; Grammer, Leslie C.; Harris, Kathleen E.; Kern, Robert; Schleimer, Robert P.

In: Journal of Allergy and Clinical Immunology, Vol. 125, No. 2, 01.01.2010.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Evidence for altered activity of the IL-6 pathway in chronic rhinosinusitis with nasal polyps

AU - Peters, Anju T.

AU - Kato, Atsushi

AU - Zhang, Ning

AU - Conley, David B.

AU - Suh, Lydia

AU - Tancowny, Brian

AU - Carter, Derek

AU - Carr, Tara

AU - Radtke, Michael

AU - Hulse, Kathryn E.

AU - Seshadri, Sudarshan

AU - Chandra, Rakesh

AU - Grammer, Leslie C.

AU - Harris, Kathleen E.

AU - Kern, Robert

AU - Schleimer, Robert P.

PY - 2010/1/1

Y1 - 2010/1/1

N2 - Background: IL-6 activates TH17 cells and regulates the response of B lymphocytes and regulatory T cells. The IL-6 receptor and the membrane protein, glycoprotein 130 (gp130), form an active signaling complex that signals through signal transducer and activator of transcription 3 (STAT3) and other signaling molecules. Both the IL-6 receptor (IL-6R) and gp130 can be found in soluble forms that regulate the pathway. Objective: We measured IL-6 signaling components and IL-17 in chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), CRS without nasal polyps (CRSsNP), and controls to assess the IL-6 pathway in CRS. Methods: IL-6, soluble IL-6R, soluble gp130 (sgp130), and IL-17 were measured in sinus tissue extracts and in nasal lavage fluid by either cytokine bead array or ELISA. phosphoSTAT3 (p-STAT3) was determined by Western blot and by immunohistochemistry. Results: IL-6 protein was significantly (P < .001) increased in CRSwNP compared with CRSsNP and controls. Soluble IL-6R was also increased in nasal polyp compared with control tissue (P < .01). Despite elevated IL-6 and sIL-6R, IL-17A, E, and F were undetectable in the sinus tissue from most of the patients with CRS and controls. p-STAT3 levels were reduced in the polyp tissue, possibly indicating reduced activity of IL-6 in the tissue. sgp130 was elevated in CRSwNP compared with CRSsNP and controls. Conclusion: p-STAT3 levels are decreased in CRSwNP despite increased levels of IL-6 and sIL-6R and are associated with the absence of an IL-17 response. This may be a response to elevated levels of sgp130, a known inhibitor of IL-6 signaling. These results indicate that IL-6 and its signaling pathway may be altered in CRSwNP.

AB - Background: IL-6 activates TH17 cells and regulates the response of B lymphocytes and regulatory T cells. The IL-6 receptor and the membrane protein, glycoprotein 130 (gp130), form an active signaling complex that signals through signal transducer and activator of transcription 3 (STAT3) and other signaling molecules. Both the IL-6 receptor (IL-6R) and gp130 can be found in soluble forms that regulate the pathway. Objective: We measured IL-6 signaling components and IL-17 in chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), CRS without nasal polyps (CRSsNP), and controls to assess the IL-6 pathway in CRS. Methods: IL-6, soluble IL-6R, soluble gp130 (sgp130), and IL-17 were measured in sinus tissue extracts and in nasal lavage fluid by either cytokine bead array or ELISA. phosphoSTAT3 (p-STAT3) was determined by Western blot and by immunohistochemistry. Results: IL-6 protein was significantly (P < .001) increased in CRSwNP compared with CRSsNP and controls. Soluble IL-6R was also increased in nasal polyp compared with control tissue (P < .01). Despite elevated IL-6 and sIL-6R, IL-17A, E, and F were undetectable in the sinus tissue from most of the patients with CRS and controls. p-STAT3 levels were reduced in the polyp tissue, possibly indicating reduced activity of IL-6 in the tissue. sgp130 was elevated in CRSwNP compared with CRSsNP and controls. Conclusion: p-STAT3 levels are decreased in CRSwNP despite increased levels of IL-6 and sIL-6R and are associated with the absence of an IL-17 response. This may be a response to elevated levels of sgp130, a known inhibitor of IL-6 signaling. These results indicate that IL-6 and its signaling pathway may be altered in CRSwNP.

KW - Chronic rhinosinusitis

KW - IL-17

KW - IL-6

KW - IL-6 receptor

KW - nasal polyps

KW - phospho-STAT3

KW - soluble glycoprotein 130

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U2 - 10.1016/j.jaci.2009.10.072

DO - 10.1016/j.jaci.2009.10.072

M3 - Article

VL - 125

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

SN - 0091-6749

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