RESUMEN

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.

Asunto(s)

Infecciones por Coxsackievirus/virología , Mucina-1/metabolismo , Pancreatitis/virología , Animales , Infecciones por Coxsackievirus/genética , Infecciones por Coxsackievirus/metabolismo , Modelos Animales de Enfermedad , Enterovirus Humano B , Inflamación/genética , Inflamación/metabolismo , Inflamación/virología , Ratones , Ratones Noqueados , Mucina-1/genética , Pancreatitis/genética , Pancreatitis/metabolismo , Receptores CCR2/genética , Receptores CCR2/metabolismo