TY - JOUR
T1 - Cytokine and chemokine production by human pancreatic islets upon enterovirus infection
AU - Schulte, Barbara M
AU - Lanke, Kjerstin H W
AU - Piganelli, Jon D
AU - Kers-Rebel, Esther D
AU - Bottino, Rita
AU - Trucco, Massimo
AU - Huijbens, Richard J F
AU - Radstake, Timothy R D J
AU - Engelse, Marten A
AU - de Koning, Eelco J P
AU - Galama, Jochem M
AU - Adema, Gosse J
AU - van Kuppeveld, Frank J M
PY - 2012/8
Y1 - 2012/8
N2 - Enteroviruses of the human enterovirus B species (HEV-Bs) (e.g., coxsackie B viruses [CVBs] and echoviruses) have been implicated as environmental factors that trigger/accelerate type 1 diabetes, but the underlying mechanism remains elusive. The aim of this study was to gain insight into the cytokines and chemokines that are produced by human pancreatic islets upon infection with CVBs. To this end, we studied the response of human islets of Langerhans upon mock or CVB3 infection. Using quantitative PCR, we showed that upon CVB3 infection, transcription of interferon (IFN), IFN-stimulated genes, and inflammatory genes was induced. Analysis of secreted cytokines and chemokines by Luminex technology confirmed production and secretion of proinflammatory cytokines (e.g., interleukin [IL]-6 and tumor necrosis factor-α) as well as various chemotactic proteins, such as IFN-γ-induced protein 10, macrophage inflammatory protein (MIP)-1α, MIP-1β, and IL-8. Infection with other HEV-Bs induced similar responses, yet their extent depended on replication efficiency. Ultra violet-inactivated CVB3 did not induce any response, suggesting that virus replication is a prerequisite for antiviral responses. Our data represent the first comprehensive overview of inflammatory mediators that are secreted by human islets of Langerhans upon CVB infection and may shed light on the role of enteroviruses in type 1 diabetes pathogenesis.
AB - Enteroviruses of the human enterovirus B species (HEV-Bs) (e.g., coxsackie B viruses [CVBs] and echoviruses) have been implicated as environmental factors that trigger/accelerate type 1 diabetes, but the underlying mechanism remains elusive. The aim of this study was to gain insight into the cytokines and chemokines that are produced by human pancreatic islets upon infection with CVBs. To this end, we studied the response of human islets of Langerhans upon mock or CVB3 infection. Using quantitative PCR, we showed that upon CVB3 infection, transcription of interferon (IFN), IFN-stimulated genes, and inflammatory genes was induced. Analysis of secreted cytokines and chemokines by Luminex technology confirmed production and secretion of proinflammatory cytokines (e.g., interleukin [IL]-6 and tumor necrosis factor-α) as well as various chemotactic proteins, such as IFN-γ-induced protein 10, macrophage inflammatory protein (MIP)-1α, MIP-1β, and IL-8. Infection with other HEV-Bs induced similar responses, yet their extent depended on replication efficiency. Ultra violet-inactivated CVB3 did not induce any response, suggesting that virus replication is a prerequisite for antiviral responses. Our data represent the first comprehensive overview of inflammatory mediators that are secreted by human islets of Langerhans upon CVB infection and may shed light on the role of enteroviruses in type 1 diabetes pathogenesis.
KW - Chemokines
KW - Coxsackievirus Infections
KW - Cytokines
KW - Diabetes Mellitus, Type 1
KW - Enterovirus B, Human
KW - Humans
KW - Islets of Langerhans
U2 - 10.2337/db11-1547
DO - 10.2337/db11-1547
M3 - Article
C2 - 22596052
SN - 0012-1797
VL - 61
SP - 2030
EP - 2036
JO - Diabetes
JF - Diabetes
IS - 8
ER -