NF-kappaB activation precedes increases in mRNA encoding neurokinin-1 receptor, proinflammatory cytokines, and adhesion molecules in dextran sulfate sodium-induced colitis in rats.
Nuclear factor kappa B (NF-kappa B) plays a key role in initiating inflammation associated with colitis. A systematic study was conducted in the rat DSS colitis model to determine the temporal relationship between NF-kappa B activation and expression of substance P (SP), neurokinin-1 receptor (NK-1R), proinflammatory cytokines, and adhesion molecules. Rats were given 5% DSS in their water and sacrificed daily for 6 days. Colon tissue was collected for assessment of histological changes, NF-kappa B activation, myeloperoxidase (MPO) activity, and expression of NK-1R, SP, TNFalpha, IL-1beta, VCAM-1, ICAM-1, E-selectin, CINC-1, MIP-1alpha, and iNOS. NF-kappa B activation increased, biphasically, on Day 1 and again on Days 4-6. The mRNA levels for ICAM-1, CINC-1, IL-1beta, TNFalpha, VCAM-1, and NK-1R rose significantly (P < 0.05) by 2-4 days. Increased iNOS mRNA levels, MPO activity, and mucosal damage occurred on Day 6. These data demonstrate that NF-kappa B activation substantially precedes the onset of physical disease signs and active inflammation.
Reed
Karen L
KL
Department of Surgery, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Fruin
A Brent
AB
Gower
Adam C
AC
Gonzales
Kelly D
KD
Stucchi
Arthur F
AF
Andry
Christopher D
CD
O'Brien
Michael
M
Becker
James M
JM
D000704:Analysis of Variance; D000818:Animals; D001483:Base Sequence; D001707:Biopsy, Needle; D003092:Colitis / Q000473:pathology* / Q000503:physiopathology*; D016207:Cytokines / Q000378:metabolism*; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000032:analysis; D008297:Male; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000032:analysis / Q000378:metabolism*; D011336:Probability; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D013373:Substance P / Q000378:metabolism
D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D012333:RNA, Messenger; D018040:Receptors, Neurokinin-1; D013373:Substance P; D016264:Dextran Sulfate