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IL-25-induced activation of nasal fibroblast and its association with the remodeling of chronic rhinosinusitis with nasal polyposis.

Abstract Interleukin (IL)-25 has been shown to play an important role in the pathogenesis of chronic rhinosinusitis with nasal polyps. Nasal polyps are associated with chronic inflammation of the mucous membranes in the paranasal sinuses and are involved in extracellular matrix (ECM) accumulation. The aim of this study is to evaluate the effects of IL-25 on myofibroblast differentiation, ECM production and the expression of matrix metalloproteinases in nasal polyp derived fibroblasts (NPDFs) and to determine the molecular mechanism underlying these processes.
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Authors

Mayor MeshTerms
Keywords
Journal Title plos one
Publication Year Start




PMID- 28771607
OWN - NLM
STAT- MEDLINE
DA  - 20170803
DCOM- 20170828
LR  - 20170828
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 12
IP  - 8
DP  - 2017
TI  - IL-25-induced activation of nasal fibroblast and its association with the
      remodeling of chronic rhinosinusitis with nasal polyposis.
PG  - e0181806
LID - 10.1371/journal.pone.0181806 [doi]
AB  - BACKGROUND AND OBJECTIVE: Interleukin (IL)-25 has been shown to play an important
      role in the pathogenesis of chronic rhinosinusitis with nasal polyps. Nasal
      polyps are associated with chronic inflammation of the mucous membranes in the
      paranasal sinuses and are involved in extracellular matrix (ECM) accumulation.
      The aim of this study is to evaluate the effects of IL-25 on myofibroblast
      differentiation, ECM production and the expression of matrix metalloproteinases
      in nasal polyp derived fibroblasts (NPDFs) and to determine the molecular
      mechanism underlying these processes. MATERIALS AND METHODS: A total of 40
      patients were enrolled in this study for Immunofluorescence studies. Expression
      of IL17 receptor B was evaluated by real time reverse transcription polymerase
      chain reaction (PCR) in NPDFs. NPDFs were stimulated with IL-25 for 48 h in the
      presence or absence of mitogen-activated protein kinase (MAPK) and NF-kappaB
      inhibitors or small interfering RNAs (siRNA). The protein levels of fibrosis
      active mediators were examined using western blotting. Fibroblast migration was
      evaluated with a scratch assay. The total collagen amount was analyzed with the
      Sircol collagen assay. RESULTS: IL-25 induced alpha-SMA, fibronectin, and MMP-1
      and -13, which were dependent on IL-17RB. IL-25 also induced activation of
      NF-kappaB and mitogen-activated protein kinase (MAPKs). By using the specific
      inhibitor of ERK, p38, JNK and NF-kappaB (U, SB, SP and Bay), we found that
      IL-25-induced expressions of alpha-SMA, fibronectin, and MMPs was regulated by
      the signaling pathways of MAPKs and NF-kappaB. IL-25 also induces alpha-SMA,
      fibronectin, and MMPs expression through IL-17RB-dependent pathways in NPDFs. The
      increased migration ability induced by IL-25 was suppressed by the specific
      inhibitors of MAPKs and NF-kappaB. CONCLUSION: Our data indicate that IL-25
      induced myofibroblast differentiation, fibronectin production, and MMP-1 and -13 
      expressions through the signaling pathways of MAPKs and NF-kappaB. in NPDFs and
      increased expression of IL-25 were also involved in the pathogenesis of nasal
      polyposis by affecting nasal fibroblasts in chronic rhinosinusitis with nasal
      polyps.
FAU - Park, Soo-Kyoung
AU  - Park SK
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, Research Institute for
      Medical Science, Chungnam National University School of Medicine, Daejeon, Korea.
FAU - Jin, Yong-De
AU  - Jin YD
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, Yanbian University
      Hospital, Yanji, China.
FAU - Park, Yeong-Kyu
AU  - Park YK
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, Research Institute for
      Medical Science, Chungnam National University School of Medicine, Daejeon, Korea.
FAU - Yeon, Sun-Hee
AU  - Yeon SH
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, Research Institute for
      Medical Science, Chungnam National University School of Medicine, Daejeon, Korea.
FAU - Xu, Jun
AU  - Xu J
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, Research Institute for
      Medical Science, Chungnam National University School of Medicine, Daejeon, Korea.
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, Yanbian University
      Hospital, Yanji, China.
FAU - Han, Rui-Ning
AU  - Han RN
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, Research Institute for
      Medical Science, Chungnam National University School of Medicine, Daejeon, Korea.
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, Yanbian University
      Hospital, Yanji, China.
FAU - Rha, Ki-Sang
AU  - Rha KS
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, Research Institute for
      Medical Science, Chungnam National University School of Medicine, Daejeon, Korea.
FAU - Kim, Yong-Min
AU  - Kim YM
AUID- ORCID: http://orcid.org/0000-0001-5414-8332
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, Research Institute for
      Medical Science, Chungnam National University School of Medicine, Daejeon, Korea.
LA  - eng
PT  - Journal Article
DEP - 20170803
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Actins)
RN  - 0 (Fibronectins)
RN  - 0 (IL-25 receptor protein, human)
RN  - 0 (Interleukin-17)
RN  - 0 (NF-kappa B)
RN  - 0 (Receptors, Interleukin)
RN  - 0 (Receptors, Interleukin-17)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.4.24.- (Matrix Metalloproteinase 13)
RN  - EC 3.4.24.7 (Matrix Metalloproteinase 1)
SB  - IM
MH  - Actins/metabolism
MH  - Adult
MH  - Cell Differentiation/drug effects
MH  - Cell Movement/drug effects
MH  - Enzyme Activation/drug effects
MH  - Female
MH  - Fibroblasts/*drug effects/*pathology
MH  - Fibronectins/biosynthesis
MH  - Gene Expression Regulation, Enzymologic/drug effects
MH  - Humans
MH  - Interleukin-17/*pharmacology
MH  - Male
MH  - Matrix Metalloproteinase 1/metabolism
MH  - Matrix Metalloproteinase 13/metabolism
MH  - Middle Aged
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - NF-kappa B/metabolism
MH  - Nasal Polyps/*complications
MH  - Nose/*pathology
MH  - Receptors, Interleukin/genetics
MH  - Receptors, Interleukin-17/metabolism
MH  - Signal Transduction/drug effects
MH  - Sinusitis/genetics/metabolism/*pathology
PMC - PMC5542454
EDAT- 2017/08/05 06:00
MHDA- 2017/08/29 06:00
CRDT- 2017/08/04 06:00
PHST- 2017/01/02 [received]
PHST- 2017/07/09 [accepted]
AID - 10.1371/journal.pone.0181806 [doi]
AID - PONE-D-17-00072 [pii]
PST - epublish
SO  - PLoS One. 2017 Aug 3;12(8):e0181806. doi: 10.1371/journal.pone.0181806.
      eCollection 2017.