Synergistic effect of κ-carrageenan on oxazolone-induced inflammation in BALB/c mice.
BACKGROUND
Carrageenan is a traditional ingredient that has been widely used in the food industry. In the present study, we propose a hypothesis that carrageenan is a conditional inflammatory agent. When the intestinal tract is in an "unhealthy" state such as that during bacterial infection or acute inflammation, carrageenan can synergistically enhance the inflammatory response.


METHODS
BALB/C mice received κ-carrageenan via intragastric administration prior to the induction of oxazolone colitis. Weight changes, survival rate, histologic change, secretion of inflammatory cytokines, ratio of regulatory T cells (Tregs) in peripheral blood, and expression of genes and proteins involved in inflammation and cell proliferation in the colonic mucosa were examined.


RESULTS
Intragastric administration of κ-carrageenan to BALB/c mice prior to the induction of oxazolone colitis resulted in an aggravation of body weight loss, a decrease in the survival ratio, aggravation of colonic inflammation, and decrease in the ratio of CD4 + CD25+/CD4+. The secretion of interleukin-4 (IL-4), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) also significantly increased after κ-carrageenan administration. κ-Carrageenan, together with oxazolone, suppressed the expression of forkhead box p3 (FOXp3) and increased the expression of Toll-like receptor 4 (TLR4), Nuclear factor-κB (NF-κB), and proliferating cell nuclear antigen in the colonic mucosa. These results were confirmed by qRT-PCR and western blot analyses at the molecular and protein levels, respectively.


CONCLUSIONS
κ-Carrageenan aggravated oxazolone-induced intestinal inflammation in BALB/c mice. This effect is associated with an activation of the TLR4-NF-κB pathway, a decreased ratio of Tregs, and the induction of Th2-dependent immune responses.
['Wu|Wei|W|', 'Wang|Feng|F|', 'Gao|Xin|X|', 'Niu|Tingting|T|', 'Zhu|Xiaojuan|X|', 'Yan|Xiaojun|X|', 'Chen|Haimin|H|']
D000276:Adjuvants, Immunologic D000818:Animals D015153:Blotting, Western D002351:Carrageenan D049109:Cell Proliferation D003092:Colitis D003106:Colon D016207:Cytokines D004357:Drug Synergism D051858:Forkhead Transcription Factors D007249:Inflammation D016753:Interleukin-10 D015847:Interleukin-4 D015850:Interleukin-6 D007413:Intestinal Mucosa D051379:Mice D008807:Mice, Inbred BALB C D016328:NF-kappa B D010081:Oxazolone D018809:Proliferating Cell Nuclear Antigen D060888:Real-Time Polymerase Chain Reaction D020133:Reverse Transcriptase Polymerase Chain Reaction D051197:Toll-Like Receptor 4 D014409:Tumor Necrosis Factor-alpha
κ-carrageenan Oxazolone Aggravation Intestinal inflammation