title: Impact of mitomycin C on the mRNA expression signatures of immunological biomarkers in eosinophilic nasal polyposis.
abstract: BACKGROUND
  The topical application of mitomycin C has been evaluated as a complementary therapy for eosinophilic nasal polyposis (ENP). However, the mechanism underlying the additional benefits of mitomycin C for the control of eosinophilic inflammation and prevention of  posttherapeutic relapse remains to be elucidated. In this work, the aim was to characterize the gene expression profile by quantitative real-time polymerase chain reaction (qPCR) of proinflammatory and regulatory biomarkers that are typically associated with ENP and to assess the impact of  the topical application of mitomycin C on the nasal mucosal tissue immunologic milieu after ENP surgery.
  
  
  METHODS
  We have selected 20 patients with ENP that were recommended to undergo surgical intervention. Normal mucosal tissue was obtained from healthy nasal mucosa from  six patients with absence of eosinophilic infiltration. To test the effect of mitomycin C, one side of the maxillary sinus mucosa was selected for topical application of this drug and the other received no further treatment and acted as the control. The genes interleukin-4 (IL-4), IL-5,  IL-10, IL-13, chemokine (C-C motif) ligand 5 (CCL5), CCL24, colony-stimulating factor 2 (CSF2), transforming growth factor beta 1 (TGFB1), tumor necrosis factor alpha (TNF-alpha), and beta actin (ACTB) were selected for gene expression  analysis by qPCR.
  
  
  RESULTS
  The data showed higher expression of proinflammatory biomarkers and lower levels of regulatory TGFB1 transcripts in ENP mucosal tissue. Surgery with topical application of mitomycin C induced a prominent transcriptional down-regulation  of the immunologic biomarkers, CCL24, TNF-alpha, CSF2, and IL-5, in ENP mucosal tissue. Additionally, this treatment restored the levels of chemokines and cytokines to those observed in the nasal mucosal tissue of control subjects, except for TGFB1, which  remained below the reference pattern. Moreover, CSF2 was identified as a putative biomarker with significant predictive value for complementary prophylactic purposes after surgery in ENP patients.
  
  
  CONCLUSIONS
  After the characterization of the expression signatures  of immunologic biomarkers in ENP, we observed that the topical use of mitomycin C is important for the reestablishment of the immunologic microenvironment of a normal expression profile of biomarkers involved in ENP mucosal tissue.
authors: Departamento de Oftalmologia, Otorrinolaringologia e Fonoaudiologia da Universidade Federal de Minas Gerais, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Alfredo Balena, Belo Horizonte, Minas Gerais, Brazil.
authors: Mirian Cabral Moreira
authors: MC
authors: de Castro
authors: Fabiana
authors: F
authors: Rocha-Silva
authors: Luciana Inácia
authors: LI
authors: Gomes
authors: Danielle Alves Gomes
authors: DA
authors: Zauli
authors: Marina
authors: M
authors: de Moraes Mourão
authors: Mariana Moreira
authors: MM
authors: de Castro
authors: Roberto Eustáquio Santos
authors: RE
authors: Guimarães
authors: Andrea
authors: A
authors: Teixeira-Carvalho
authors: Olindo Assis
authors: OA
authors: Martins-Filho
mesh_terms: D000287:Administration, Topical; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D015415:Biomarkers / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D000529:Complementary Therapies; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004804:Eosinophils / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007377:Interleukin-3 / Q000235:genetics / Q000378:metabolism; D016685:Mitomycin / Q000008:administration & dosage*; D009297:Nasal Mucosa / Q000187:drug effects* / Q000276:immunology / Q000601:surgery; D009298:Nasal Polyps / Q000188:drug therapy* / Q000276:immunology / Q000601:surgery; D012333:RNA, Messenger / Q000032:analysis; D059467:Transcriptome
chemical_list: D000903:Antibiotics, Antineoplastic; D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D007377:Interleukin-3; D012333:RNA, Messenger; D016685:Mitomycin