Riboflavin inhibits IL-6 expression and p38 activation in islet cells.
Riboflavin is a water-soluble vitamin that reduces the production of proinflammatory mediators and oxygen radicals. Because islet beta-cells are very sensitive to oxidative stress and to cytokines, we investigated the possible cytoprotective effects of riboflavin on insulinoma NIT-1 cells and on isolated rodent islets. NIT-1 cells and islets cultured in the presence or absence of 10 microM riboflavin were studied at baseline and after exposure to cytokines (TNF-alpha, IL-1beta, INF-gamma). Riboflavin treatment did not affect islet cell viability as assessed by flow cytometry for caspases activation. However, riboflavin prevented the cytokine-induced increase in IL-6 mRNA expression and p38 phosphorylation analyzed by real-time PCR and immunoassay, respectively. In summary, nontoxic doses of riboflavin prevent cytokines-induced p38 phosphorylation and IL-6 upregulation in islet cells. This observation, together with the safety profile of riboflavin in the clinical setting, makes it an appealing agent for islet cytoprotection in islet transplantation protocols.
Cobianchi
Lorenzo
L
Cell Transplant Center, Diabetes Research Institute, Leonard M. Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
Fornoni
Alessia
A
Pileggi
Antonello
A
Molano
R Damaris
RD
Sanabria
Nahir Y
NY
Gonzalez-Quintana
Jorge
J
Bocca
Nicola
N
Marzorati
Simona
S
Zahr
Elsie
E
Hogan
Anthony R
AR
Ricordi
Camillo
C
Inverardi
Luca
L
D000818:Animals; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000628:therapy; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects*; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D016381:Islets of Langerhans Transplantation; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D051381:Rats; D012256:Riboflavin / Q000378:metabolism / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; D012256:Riboflavin