Effect of short-term, low dose aspirin supplementation on the activation of pro-inflammatory NF-kappaB in aged rats.
The basis of our recently proposed "molecular inflammation theory of aging" is that activated inflammatory transcription factors, including versatile NF-kappaB, occur widespread in the organism during aging. NF-kappaB plays a key role in pro-inflammatory gene expression, such as cyclooxygenase (COX). Aspirin is one of the most commonly used non-steroidal anti-inflammatory drugs because of its ability to inhibit COX activity. Thus, in the present study, we investigated the effect of short-term, low dose aspirin intake on the modulation of pro-inflammatory NF-kappaB activation in old rats. To conduct the study, 24-month-old Fischer 344 rats were supplemented with low dose aspirin (0.015%) for 10 days. Biochemical analyses showed suppressed reactive species (RS) and COX-2 activity. The data also showed that NF-kappaB activation and its associated gene expressions, such as COX-2, iNOS, VCAM-1 and ICAM-1, were all suppressed by the low dose aspirin supplementation through the inhibition of phosphorylation and degradation of IkappaBalpha via the NIK/IKK pathway. Our molecular exploration further revealed that aspirin's suppressive action of NF-kappaB was mediated by its ability to inhibit the nuclear translocation of cytosolic thioredoxin and redox factor-1. These findings showed for the first time that in aged rat short-term low dose dietary aspirin feeding modulates the molecular signal transduction involved in the inflammatory process.
Jung
Kyung Jin
KJ
Department of Pharmacy, College of Pharmacy, Aging Tissue Bank, Pusan National University, Gumjung-gu, Busan 609 735, Republic of Korea.
Kim
Ji Young
JY
Zou
Yani
Y
Kim
You Jung
YJ
Yu
Byung Pal
BP
Chung
Hae Young
HY
D000375:Aging / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D001241:Aspirin / Q000008:administration & dosage*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016328:NF-kappa B; D001241:Aspirin