Reduced expression of antimicrobial <scp>PLUNC</scp> proteins in nasal polyp tissues of patients with chronic rhinosinusitis

Seshadri, Sudarshan; Lin, David C.; Rosati, Mariel G.; Carter, Roderick G.; Norton, James E.; Suh, Lydia; Kato, Atsushi; Chandra, Rakesh K.; Harris, Kathleen E.; Chu, Hong Wei; Peters, Anju T.; Tan, Bruce K.; Conley, David B.; Grammer, Leslie C.; Kern, Robert C.; Schleimer, Robert P.

doi:10.1111/j.1398-9995.2012.02848.x

Cited by 95 publications

(101 citation statements)

References 35 publications

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“…This suggests that low levels of plasminogen activators might confer an increased susceptibility to excess fibrin deposition in UT and may provide an explanation of why NP arise from mucous membranes in and around the middle nasal meatus but not in the IT. In previous studies, we have found that IT and UT differ dramatically in levels of host defense molecules, so such a regional difference is not unprecedented (36,37).…”

Section: Discussionmentioning

confidence: 86%

Excessive Fibrin Deposition in Nasal Polyps Caused by Fibrinolytic Impairment through Reduction of Tissue Plasminogen Activator Expression

Takabayashi

Kato²,

Peters³

et al. 2013

Am J Respir Crit Care Med

148

205

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Rationale: Nasal polyps (NPs) are characterized by intense edema or formation of pseudocysts filled with plasma proteins, mainly albumin. However, the mechanisms underlying NP retention of plasma proteins in their submucosa remain unclear. Objectives: We hypothesized that formation of a fibrin mesh retains plasma proteins in NPs. We assessed the fibrin deposition and expression of the components of the fibrinolytic system in patients with chronic rhinosinusitis (CRS). Methods:We assessed fibrin deposition in nasal tissue from patients with CRS and control subjects by means of immunofluorescence. Fibrinolytic components, d-dimer, and plasminogen activators were measured using ELISA, real-time PCR, and immunohistochemistry. We also performed gene expression and protein quantification analysis in cultured airway epithelial cells. Measurements and Main Results: Immunofluorescence data showed profound fibrin deposition in NP compared with uncinate tissue (UT) from patients with CRS and control subjects. Levels of the cross-linked fibrin cleavage product protein, d-dimer, were significantly decreased in NP compared with UT from patients with CRS and control subjects, suggesting reduced fibrinolysis (P , 0.05). Expression levels of tissue plasminogen activator (t-PA) mRNA and protein were significantly decreased in NP compared with UT from patients with CRS and control subjects (P , 0.01). Immunohistochemistry demonstrated clear reduction of t-PA in NP, primarily in the epithelium and glands. Th2 cytokine-stimulated cultured airway epithelial cells showed down-regulation of t-PA, suggesting a potential Th2 mechanism in NP. Conclusions: A Th2-mediated reduction of t-PA might lead to excessive fibrin deposition in the submucosa of NP, which might contribute to the tissue remodeling and pathogenesis of CRS with nasal polyps.

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Section: Discussionmentioning

confidence: 86%

Excessive Fibrin Deposition in Nasal Polyps Caused by Fibrinolytic Impairment through Reduction of Tissue Plasminogen Activator Expression

Takabayashi

Kato²,

Peters³

et al. 2013

Am J Respir Crit Care Med

148

205

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“…Decreased expression of some host defense molecules has been associated with CRS. 334,[519][520][521] A precise molecular pathway for this defect has not been proposed, but the cytokine IL-22 and its receptor IL-22R are key regulators of mucosal host defense, 522 acting in large part through the transcription factor STAT 3. 523,524 Diminished expression of IL-22R 525 and blunting of the STAT 3 pathway 526 have been reported; these defects appear to be associated with CRS broadly, and are not specific for the presence or absence of NPs.…”

Section: Discussionmentioning

confidence: 99%

International Consensus Statement on Allergy and Rhinology: Rhinosinusitis

Orlandi

Kingdom

Hwang

et al. 2016

Int Forum Allergy Rhinol

559

888

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Background:The body of knowledge regarding rhinosinusitis (RS) continues to expand, with rapid growth in number of publications, yet substantial variability in the quality of those presentations. In an effort to both consolidate and critically appraise this information, rhinologic experts from around the world have produced the International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR:RS). Methods:Evidence-based reviews with recommendations (EBRRs) were developed for scores of topics, using previously reported methodology. Where existing evidence was insufficient for an EBRR, an evidence-based review (EBR) was produced. The sections were then synthesized and the entire manuscript was then reviewed by all authors for consensus. Results:The resulting ICAR:RS document addresses multiple topics in RS, including acute RS (ARS), chronic RS (CRS) with and without nasal polyps (CRSwNP and CRSsNP), recurrent acute RS (RARS), acute exacerbation of CRS (AE-CRS), and pediatric RS. Conclusion:As a critical review of the RS literature, ICAR:RS provides a thorough review of pathophysiology and evidence-based recommendations for medical and surgical treatment. It also demonstrates the significant gaps in our understanding of the pathophysiology and optimal management of RS. Too o en the foundation upon which these recommendations are based is comprised of lowerlevel evidence. It is our hope that this summary of the evidence in RS will point out where additional research efforts may be directed. C 2016 ARS-AAOA, LLC. Key Words:rhinosinusitis; chronic rhinosinusitis; acute rhinosinusitis; recurrent acute rhinosinusitis; evidence-based medicine; systematic review; endoscopic sinus surgery List of Abbreviations Used

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“…In recent years, some studies point out that SPLUNC1 has a close relationship with the inflammatory response. For example, SPLUNC1 was able to regulate Pseudomonas aeruginosa-induced lung inflammation in mice (9), and was found to be markedly downregulated in patients with chronic sinusitis (10). SPLUNC1 was found to modulate the inflammatory response to resist pulmonary inhaled particles by increasing leukocyte recruitment and phagocytic activity (11).…”

Section: Introductionmentioning

confidence: 99%

SPLUNC1 reduces the inflammatory response of nasopharyngeal carcinoma cells infected with the EB virus by inhibiting the TLR9/NF-κB pathway

Ou¹,

Sun²,

Zhang³

et al. 2015

Oncology Reports

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Abstract. Studies indicate that the natural immune-related protein short palate, lung, and nasal epithelium clone 1 (SPLUNC1) plays an antitumor role in nasopharyngeal epithelial tissue. However, the detailed mechanism of the tumor-suppressor effect of SPLUNC1 in the inflammatory microenvironment of Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) remains elusive. The aim of the present study was to explore how SPLUNC1 reduces the inflammatory response of NPC cells infected with EBV by regulating the Toll-like receptor (TLR)9/NF-κB signaling pathway. As detected by immunohistochemistry and western blotting, SPLUNC1 protein expression exhibited low or negative expression in the NPC epithelial samples/cells, while it demonstrated positive expression in normal nasopharyngeal epithelial tissues/cells; this pattern of expression was the contrary to that of TLR9. The poorly differentiated HNE2 cell line had the highest efficiency of transfer of infection with EBV by 'cell-to-cell' contact method. The group of EBV-infected HNE2 cells showed significantly higher activation of the expression of TLR9/NF-κB signaling pathway-associated factors (TLR9, CD14, MyD88, IKK, P-IKβα, P-NF-κB and NF-κB). The levels of inflammatory cytokines IL-6, IL-8, IL-1β and TNF-α in the HNE2 cell group after EBV infection were higher than these levels in the uninfected cell group (P<0.05); Meanwhile, after EBV infection, the expression levels of TLR9/NF-κB pathway associated-protein and inflammatory cytokines IL-6, IL-8, IL-1β and TNF-α in the HNE2/SPLUNC1 cell group were lower than these levels in the HNE2/Vector cell group (P<0.05). After EBV-DNA direct transfection, cytokine mRNA expression levels of TLR9, IL-6, IL-8, IL-1β and TNF-α in the HNE2 cell group were significantly higher than these levels in the NP69 cell group (P<0.05). The expression levels of these cytokines in the HNE2/SPLUNC1 cell group were obviously lower than these levels in the HNE2/Vector cell group (P<0.05). These results suggest that EBV infection of NPC cells can activate the TLR9/ NF-κB signaling pathway, promote the release of inflammatory cytokines and consequently enhance the inflammatory response, while SPLUNC1 can weaken the inflammatory response induced by EBV infection in NPC cells through the regulation of the TLR9/NF-κB signaling pathway and control of the tumor inflammatory microenvironment.

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Reduced expression of antimicrobial PLUNC proteins in nasal polyp tissues of patients with chronic rhinosinusitis

Cited by 95 publications

References 35 publications

Excessive Fibrin Deposition in Nasal Polyps Caused by Fibrinolytic Impairment through Reduction of Tissue Plasminogen Activator Expression

Excessive Fibrin Deposition in Nasal Polyps Caused by Fibrinolytic Impairment through Reduction of Tissue Plasminogen Activator Expression

International Consensus Statement on Allergy and Rhinology: Rhinosinusitis

SPLUNC1 reduces the inflammatory response of nasopharyngeal carcinoma cells infected with the EB virus by inhibiting the TLR9/NF-κB pathway

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