PMID- 29341450
OWN - NLM
STAT- MEDLINE
DCOM- 20190729
LR  - 20190729
IS  - 2042-6984 (Electronic)
IS  - 2042-6976 (Print)
IS  - 2042-6976 (Linking)
VI  - 8
IP  - 4
DP  - 2018 Apr
TI  - Characterization of a novel, papain-inducible murine model of eosinophilic 
      rhinosinusitis.
PG  - 513-521
LID - 10.1002/alr.22072 [doi]
AB  - BACKGROUND: Eosinophilic chronic rhinosinusitis (ECRS) is a disease characterized 
      by eosinophilic inflammatory infiltrate and a local type 2 cytokine milieu. 
      Current animal models fail to recapitulate many of the innate and adaptive 
      immunologic hallmarks of the disease, thus hindering the development of effective 
      therapeutics. In the present study, mice were exposed intranasally to the 
      cysteine protease papain, which shares functional similarities with parasitic 
      proteases and aeroallergens, to generate a rapidly inducible murine model of 
      eosinophilic rhinosinusitis. METHODS: C57BL/6 mice were intranasally instilled 
      with 20 mug papain or heat-inactivated papain (HP) on days 0-2 and days 7-10, and 
      then euthanized on day 11. Nasal lavage fluid (NALF) was analyzed to quantify 
      eosinophils and inflammatory cytokine secretion. Sinonasal tissue was sectioned 
      and stained for goblet cells or homogenized to analyze cytokine levels. Serum 
      samples were assayed for immunoglobulin E (IgE) by enzyme-linked immunoassay. 
      Sinonasal mucosal tissue was dissociated and analyzed by flow cytometry. RESULTS: 
      Compared with HP treatment, papain induced significant eosinophilia in NALF, 
      goblet cell hyperplasia, innate and adaptive immune cell infiltration, type 2 
      cytokine production, and IgE responses. Flow cytometric analysis of sinonasal 
      tissues revealed significant inflammatory cell infiltration and 
      interleukin-13-producing cell populations. CONCLUSION: In this study, we 
      demonstrated that the cysteine protease papain induces allergic sinonasal 
      eosinophilic rhinosinusitis and resembles T-helper 2 cell inflammation and innate 
      immune characteristics of ECRS. This model permits further study into the 
      molecular mechanisms underlying ECRS pathology and provides a model system for 
      the evaluation of potential pharmacologic interventions.
CI  - (c) 2018 ARS-AAOA, LLC.
FAU - Tharakan, Anuj
AU  - Tharakan A
AD  - Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University 
      School of Medicine, Baltimore, MD.
FAU - Dobzanski, Alex
AU  - Dobzanski A
AD  - Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University 
      School of Medicine, Baltimore, MD.
FAU - London, Nyall R Jr
AU  - London NR Jr
AD  - Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University 
      School of Medicine, Baltimore, MD.
FAU - Khalil, Syed M
AU  - Khalil SM
AUID- ORCID: 0000-0003-4346-6209
AD  - Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University 
      School of Medicine, Baltimore, MD.
FAU - Surya, Nitya
AU  - Surya N
AD  - Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University 
      School of Medicine, Baltimore, MD.
FAU - Lane, Andrew P
AU  - Lane AP
AD  - Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University 
      School of Medicine, Baltimore, MD.
FAU - Ramanathan, Murugappan Jr
AU  - Ramanathan M Jr
AD  - Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University 
      School of Medicine, Baltimore, MD.
LA  - eng
GR  - K23 ES020859/ES/NIEHS NIH HHS/United States
GR  - L30 ES022003/ES/NIEHS NIH HHS/United States
GR  - R01 AI072502/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20180117
PL  - United States
TA  - Int Forum Allergy Rhinol
JT  - International forum of allergy & rhinology
JID - 101550261
RN  - 0 (Cytokines)
RN  - EC 3.4.22.2 (Papain)
MH  - Animals
MH  - Chronic Disease
MH  - Cytokines/metabolism
MH  - *Disease Models, Animal
MH  - Eosinophils/*drug effects/metabolism
MH  - Female
MH  - Goblet Cells/pathology
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Nasal Lavage Fluid/cytology/immunology
MH  - Papain/*toxicity
MH  - Paranasal Sinuses/drug effects/pathology
MH  - Rhinitis/blood/*chemically induced/immunology/pathology
MH  - Sinusitis/blood/*chemically induced/immunology/pathology
PMC - PMC5880736
MID - NIHMS925654
OTO - NOTNLM
OT  - IL-33
OT  - epithelial barrier
OT  - papain
OT  - rhinosinusitis
EDAT- 2018/01/18 06:00
MHDA- 2019/07/30 06:00
PMCR- 2019/04/01
CRDT- 2018/01/18 06:00
PHST- 2017/08/14 00:00 [received]
PHST- 2017/11/15 00:00 [revised]
PHST- 2017/12/04 00:00 [accepted]
PHST- 2018/01/18 06:00 [pubmed]
PHST- 2019/07/30 06:00 [medline]
PHST- 2018/01/18 06:00 [entrez]
PHST- 2019/04/01 00:00 [pmc-release]
AID - 10.1002/alr.22072 [doi]
PST - ppublish
SO  - Int Forum Allergy Rhinol. 2018 Apr;8(4):513-521. doi: 10.1002/alr.22072. Epub 
      2018 Jan 17.