Mucin-1 is required for Coxsackie Virus B3-induced inflammation in pancreatitis

Xiang Liu, Dahn L Clemens, James A. Grunkemeyer, Jeffrey D. Price, Kelly O’Connell, Nora M. Chapman, Peter Storz, Haitao Wen, Jesse L. Cox, Whitney L. Reid, Michael A Hollingsworth, Sarah P Thayer

Research output: Contribution to journalArticle

Abstract

The Muc-1 oncoprotein is a tumor-associated mucin often overexpressed in pancreatic cancer. We report that knockout of Muc-1 reduced the degree of pancreatic inflammation that resulted from infection with Coxsackievirus B3 (CVB3) in a mouse model. CVB3-infected Muc-1-deficient (Muc-1KO) mice had significantly reduced infiltration of macrophages into the murine pancreas. We found that Muc-1 signaling through NF-κB increased expression of ICAM-1, a pro-inflammatory mediator that recruits macrophages. Further investigation revealed that bone marrow derived macrophages (BMDM) from the Muc-1KO mice exhibited defective migration properties, in part due to low expression of the C-C motif chemokine receptor (CCR2) and the integrin Very Late Antigen 4 (VLA-4). The results presented here provide novel insight into the role of Muc-1 in regulating the inflammatory response and the cellular microenvironment in pancreatitis.

Original languageEnglish (US)
Article number10656
JournalScientific reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

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Mucin-1
Enterovirus
Pancreatitis
Macrophages
Inflammation
CCR Receptors
Coxsackievirus Infections
Integrin alpha4beta1
Cellular Microenvironment
Oncogene Proteins
Mucins
Intercellular Adhesion Molecule-1
Pancreatic Neoplasms
Integrins
Pancreas
Neoplasms

ASJC Scopus subject areas

  • General

Cite this

Mucin-1 is required for Coxsackie Virus B3-induced inflammation in pancreatitis. / Liu, Xiang; Clemens, Dahn L; Grunkemeyer, James A.; Price, Jeffrey D.; O’Connell, Kelly; Chapman, Nora M.; Storz, Peter; Wen, Haitao; Cox, Jesse L.; Reid, Whitney L.; Hollingsworth, Michael A; Thayer, Sarah P.

In: Scientific reports, Vol. 9, No. 1, 10656, 01.12.2019.

Research output: Contribution to journalArticle

Liu, X, Clemens, DL, Grunkemeyer, JA, Price, JD, O’Connell, K, Chapman, NM, Storz, P, Wen, H, Cox, JL, Reid, WL, Hollingsworth, MA & Thayer, SP 2019, 'Mucin-1 is required for Coxsackie Virus B3-induced inflammation in pancreatitis', Scientific reports, vol. 9, no. 1, 10656. https://doi.org/10.1038/s41598-019-46933-y
Liu, Xiang ; Clemens, Dahn L ; Grunkemeyer, James A. ; Price, Jeffrey D. ; O’Connell, Kelly ; Chapman, Nora M. ; Storz, Peter ; Wen, Haitao ; Cox, Jesse L. ; Reid, Whitney L. ; Hollingsworth, Michael A ; Thayer, Sarah P. / Mucin-1 is required for Coxsackie Virus B3-induced inflammation in pancreatitis. In: Scientific reports. 2019 ; Vol. 9, No. 1.
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