interleukin-8 and Jaundice--Obstructive

Obstructive jaundice is associated with bacterial translocation and inflammatory cytokine induction. It is unknown if toll-like receptors (TLRs) and their upstream molecule high mobility group box-1 (HMGB1) are involved in the pathogenetic mechanism and if glucocorticoid is effective in modulating the process.. A rat model of cholestasis by ligation of the extrahepatic bile duct (BDL) for 2 wk was created. TLRs, interferon regulatory factors (IRFs), IL-6, IL-8, antimicrobial peptide β-defensin, and cathelicidin, as well as HMGB1 expressions were studied by using real-time quantitative reverse transcription-polymerase chain reaction, immunohistochemistry, Western blotting, and enzyme-linked immunosorbent assay (ELISA). Glucocorticoid treatment was applied to a group of BDL rats.. Obstructive jaundice for 2 wk was associated with significant up-regulation of TLR1, 2, 4, 6, 7, and 9 mRNA expressions. There were significant increases of liver IRF5, IL-6, and β-defensin 1 mRNA levels in the BDL rats than in the sham and nonoperative control rats, which were associated with significant increase of immunoreactive IRF5 protein staining in the nucleus of Kupffer cells and neutrophils. Hepatic HMGB1 expression and release into serum were significantly elevated in the cholestatic rats than in the sham and control rats. Glucocorticoid treatment significantly decreased hepatic HMGB1 expression and release into serum, which was associated with significantly decreased hepatic TLR4 mRNA expression in the cholestatic rats.. The results indicate that obstructive jaundice may induce hepatic HMGB1 expression with activation of TLR4 and a number of downstream signaling molecules, which can be reversed by glucocorticoid administration.

Topics: Active Transport, Cell Nucleus; Animals; beta-Defensins; Glucocorticoids; HMGB1 Protein; Interferon Regulatory Factors; Interleukin-8; Jaundice, Obstructive; Liver; Male; Rats; Rats, Sprague-Dawley; RNA, Messenger; Toll-Like Receptors

The objective of the study was to observe the effects of Salvia miltiorrhiza on intercellular adhesion molecule 1 (ICAM-1) protein expression in the lungs of rats with severe acute pancreatitis (SAP) or obstructive jaundice (OJ).. A total of 288 rats were used for SAP- and OJ-associated experiments. The rats were randomly divided into sham-operated, model control, and treated group. According to the difference of time points after operation, the SAP rats of each group were subdivided into 3-, 6-, and 12-hour groups, whereas the OJ rats were divided into 7-, 14-, 21-, and 28-day groups. The contents of interleukin (IL) 6, IL-18, nitric oxide, malondialdehyde, and superoxide dismutase in serum were determined, and pathological changes and ICAM-1 protein expression in the lungs were observed.. Compared with the respective model control groups, in treated groups of SAP and OJ rats, the numbers of dead rats declined; serum superoxide dismutase content significantly increased, and serum IL-18, IL-6, and malondialdehyde contents were significantly decreased; the positive staining intensity of ICAM-1 protein in the lungs decreased significantly (P < 0.05, P < 0.01, or P < 0.001); and pathological changes in the lungs were relieved.. Salvia miltiorrhiza plays a positive role in the protection of the lungs of SAP and OJ rats.

Topics: Acute Disease; Animals; Drugs, Chinese Herbal; Intercellular Adhesion Molecule-1; Interleukin-6; Interleukin-8; Jaundice, Obstructive; Lung; Malondialdehyde; Nitric Oxide; Pancreatic Diseases; Pancreatitis; Plant Preparations; Pneumonia; Rats; Salvia miltiorrhiza; Severity of Illness Index; Superoxide Dismutase