Carrageenan-induced increase in interleukin-8 secretion is modified by pre-treatment with galactosidases and carrageenases

Thumbnail Image
Bhattacharyya, S.
Liu, H.
Zhang, Z.
Jam, M.
Dudeja, P.K.
Michel, G.
Linhardt, Robert J.
Tobacman, J.
Issue Date
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Research Projects
Organizational Units
Journal Issue
Alternative Title
The common food additive carrageenan predictably induces intestinal inflammation in animal models. Mechanisms of carrageenan-induced NFκB and IL-8 stimulation include an immune-mediated pathway involving toll-like receptor 4 (TLR4) and B-cell lymphoma/leukemia 10 (BCL10) and a reactive-oxygen species (ROS)-mediated pathway. To determine how the structure of CGN contributes to its initiation of inflammation by these two distinct mechanisms, we treated carrageenans with galactosidases and carrageenases, and determined the impact on IL-8 secretion and BCL10 production. Hydrolysis of carrageenan by the enzyme α-1→(3,6)-galactosidase significantly reduced the increases in IL-8 and BCL10, but other galactosidases tested, including α-1→6-, β-1→4-, and β-1→3,6-galactosidases had no effect. In contrast, specific κ- or ι-carrageenases, which hydrolyze the β-1,4-galactosidic bonds, produced increases in IL-8 and BCL10, attributable to increased exposure of the immunogenic α-1→3-galactosidic epitope of carrageenan to TLR4. These results were consistent with induction of the innate immune response by an interaction of TLR4 with the unusual α-D-Gal-(1→3)-D-Gal epitope that is present in carrageenan. Activation of the ROS-mediated pathway was unaffected by treatment of κ-CGN with either κ-CGNase (3 mg/L), α-1→(3,6)-galactosidase (20 mU/ml), or these enzymes in combination, indicating that the changes in IL-8 production were attributable to effects on the TLR4-BCL10-mediated innate immune pathway of induction of inflammation. These findings provide new information about the specificity of the carbohydrate-protein interaction between carrageenan and TLR4 and may help to devise treatments that modify the immune reactivity induced by carbohydrate antigens.
Journal of Nutritional Biochemistry, 21, 906-913
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Full Citation
Carrageenan-induced increase in interleukin-8 secretion is modified by pre-treatment with galactosidases and carrageenases, S. Bhattacharyya, H. Liu, Z. Zhang, M. Jam, P. K. Dudeja, G. Michel, R. J. Linhardt, J. Tobacman, Journal of Nutritional Biochemistry, 21, 906-913, 2010.
Terms of Use
PubMed ID