An anti-inflammatory mechanism of taurine conjugated 5-aminosalicylic acid against experimental colitis: taurine chloramine potentiates inhibitory effect of 5-aminosalicylic acid on IL-1beta-mediated NFkappaB activation.
Previously, we reported that oral administration of taurine conjugated 5-aminosalicylic acid, a colon-specific prodrug of 5-aminosalicylic acid (5-ASA), is effective in ameliorating experimental colitis and taurine elicits an additive anti-inflammatory effect upon cotreatment with 5-ASA. To explore a molecular mechanism for the anti-inflammatory property of the prodrug, we investigated the effect of the conjugate on IL-1beta-mediated NFkappaB activation. In human colon carcinoma Caco-2 and HCT116 cells, NFkappaB activity was accessed by a luciferase reporter assay and IL-6 secretion. Protein levels were determined by Western blotting. IL-6 levels were monitored by an Elisa kit. Treatment with either 5-ASA or taurine chloramine (TauCl) inhibited IL-1beta-mediated NFkappaB dependent luciferase expression and IL-6 secretion. In HCT116 cells, the inhibitory effect by TauCl or 5-ASA was through preventing IL-1beta-induced IkappaB kinase activation and subsequently interfering with IkappaBalpha degradation and p65 nuclear accumulation. Furthermore, combined TauCl/5-ASA treatment interfered additively with the activation process, leading to additive inhibitory effect on IL-1beta-mediated NFkappaB activation. Our results suggest that the anti-inflammatory effect of the prodrug on experimental colitis is attributed to the inhibition of the IL-1beta-mediated NFkappaB activation and the taurine effect is through TauCl potentiating the ability of 5-ASA to inhibit IL-1beta dependent NFkappaB activation.
Joo
Kanghyun
K
Laboratory of Biomedicinal/Medicinal Chemistry, College of Pharmacy, Pusan National University, Busan, Republic of Korea.
Lee
Youna
Y
Choi
Deakyu
D
Han
Jeongoh
J
Hong
Sungchae
S
Kim
Young Mi
YM
Jung
Yunjin
Y
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003092:Colitis / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism*; D019804:Mesalamine / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D016328:NF-kappa B / Q000378:metabolism*; D011355:Prodrugs / Q000378:metabolism; D013654:Taurine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D016328:NF-kappa B; D011355:Prodrugs; D013654:Taurine; D019804:Mesalamine; C043410:N-chlorotaurine; D051550:I-kappa B Kinase