title: Synergistic effect of κ-carrageenan on oxazolone-induced inflammation in BALB/c mice.
abstract: 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.
authors.affiliation: Key Laboratory of Applied Marine Biotechnology of Zhejiang Province, Ningbo University, Post Box 71, Ningbo, Zhejiang, 315211, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Clinical Laboratory, Lihuili hospital of Ningbo Medical Center, Ningbo, Zhejiang, 315041, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Key Laboratory of Applied Marine Biotechnology of Zhejiang Province, Ningbo University, Post Box 71, Ningbo, Zhejiang, 315211, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Gao
authors.affiliation: Key Laboratory of Applied Marine Biotechnology of Zhejiang Province, Ningbo University, Post Box 71, Ningbo, Zhejiang, 315211, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Niu
authors.affiliation: Key Laboratory of Applied Marine Biotechnology of Zhejiang Province, Ningbo University, Post Box 71, Ningbo, Zhejiang, 315211, China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Applied Marine Biotechnology of Zhejiang Province, Ningbo University, Post Box 71, Ningbo, Zhejiang, 315211, China. yanxiaojun@nbu.edu.cn.|Collaborative Innovation Center for Zhejiang Marine High-efficiency and Healthy Aquaculture, Ningbo University, Ningbo, Zhejiang, 315211, China. yanxiaojun@nbu.edu.cn.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Yan
authors.affiliation: Key Laboratory of Applied Marine Biotechnology of Zhejiang Province, Ningbo University, Post Box 71, Ningbo, Zhejiang, 315211, China. haiminch75@hotmail.com.|Collaborative Innovation Center for Zhejiang Marine High-efficiency and Healthy Aquaculture, Ningbo University, Ningbo, Zhejiang, 315211, China. haiminch75@hotmail.com.
authors.forename: Haimin
authors.initials: H
authors.lastname: Chen
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D002351:Carrageenan / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D003092:Colitis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D003106:Colon / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D004357:Drug Synergism; D051858:Forkhead Transcription Factors / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D007249:Inflammation; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D010081:Oxazolone / Q000493:pharmacokinetics*; D018809:Proliferating Cell Nuclear Antigen / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051197:Toll-Like Receptor 4 / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000235:genetics / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D015850:Interleukin-6; D016328:NF-kappa B; D018809:Proliferating Cell Nuclear Antigen; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D010081:Oxazolone; D015847:Interleukin-4; D002351:Carrageenan
keywords: Aggravation; Intestinal inflammation; Oxazolone; κ-carrageenan