No abstract

These findings suggest that honokiol is capable of suppressing the lethal response and acute lung injury associated with sepsis, and support the potential use of honokiol as a therapeutic agent for the conditions associated with septic shock.

Severe acute pancreatitis remains a life-threatening disease with a high mortality rate among a defined proportion of those affected. Apoptosis has been hypothesized to be a beneficial form of cell death in acute pancreatitis. Honokiol, a low-molecular-weight natural product, possesses the ability of anti-inflammation and apoptosis induction. Here, we investigate whether honokiol can ameliorate severe acute pancreatitis and the associated acute lung injury in a mouse model. Mice received six injections of cerulein at 1-h intervals, then given one intraperitoneal injection of bacterial lipopolysaccharide for the induction of severe acute pancreatitis. Moreover, mice were intraperitoneally given vehicle or honokiol 10 min after the first cerulein injection. Honokiol protected against the severity of acute pancreatitis in terms of increased serum amylase and lipase levels, pancreas pathological injury, and associated acute lung injury. Honokiol significantly reduced the increases in serum tumor necrosis factor-α, interleukin 1, and nitric oxide levels 3 h and serum high-mobility group box 1 24 h after acute pancreatitis induction. Honokiol also significantly decreased myeloperoxidase activities in the pancreas and the lungs. Endoplasmic reticulum stress-related molecules eIF2α (phosphorylated) and CHOP protein expressions, apoptosis, and caspase-3 activity were increased in the pancreas of mice with severe acute pancreatitis, which was unexpectedly enhanced by honokiol treatment. These results suggest that honokiol protects against acute pancreatitis and limits the spread of inflammatory damage to the lung in a severe acute pancreatitis mouse model. The acceleration of pancreatic cell apoptosis by honokiol may play a pivotal role.

Escherichia coli is the most common cause of urinary tract infection. Elevated blood and urine interleukin-6 (IL-6) levels have been shown in inflammatory urinary tract diseases. The role of IL-6 in mediating the urodynamic dysfunction in response to E. coli-induced urinary tract infection has not yet been fully elucidated. In this study, we investigated the role of IL-6 in the nitric oxide (NO)-triggered alteration of contractile responses in the urinary bladder under an E. coli-induced inflammatory condition. The electrical field stimulation (EFS)-evoked contractions of the isolated detrusor strips, and immunoblotting for detecting protein expression in the bladders was measured short term (1 h) or long term (6 or 24 h) after intraperitoneal injection of E. coli endotoxin (lipopolysaccharide [LPS]) or intravesical instillation of human pyelonephritogenic E. coli-J96 (O4:K6) strain or LPS into mice. IL-6 and NO productions were increased in the urinary bladders of mice 1 to 24 h after LPS or E. coli-J96 treatment. Inducible NO synthase (iNOS) expression and protein kinase C (PKC) activation and EFS-evoked detrusor contractions were increased in the bladders at 6 h after LPS or E. coli-J96 treatment, which could be reversed by anti-IL-6 antibody and iNOS inhibitor aminoguanidine. At 1 h after LPS administration, bladder NO generation, endothelial NOS expression, and EFS-evoked detrusor contractions were effectively increased, whereas anti-IL-6 antibody could not reverse these LPS-induced responses. These results indicate that IL-6 may play an important role in the iNOS/NOtriggered PKC-activated contractile response in urinary bladder during E. coli or LPS-induced inflammation.Urinary tract infections have been estimated that are the common infection acquired in hospitalized adult patients with a prevalence of 1 to 10% representing 30 to 40% of all nosocomial infections (4, 10, 14, 37). The development of urinary tract infections, including cystitis and pyelonephritis, in critically ill adult patients has been associated with considerable morbidity, prolonged hospitalization, and greater healthcare expenditures (4, 10). Urinary tract infections can also be a significant source of morbidity in the pediatric population (32). Escherichia coli is the most common cause of urinary tract infection (35). Increased frequency of micturition is a common symptom of urinary tract infection (20). The exact mechanisms of the symptoms of urinary tract infection are poorly understood.Inflammation plays a role in most bladder pathologies (7,30,38). Infection of the urinary tract results in an inflammatory response characterized by increased levels of urinary cytokines and neutrophil influx (2, 6). In rodent or mouse urinary tract infection models, which involved treatment with E. coli lipopolysaccharide (LPS) by intravesical instillation or intraperitoneal injection, induced interleukin-6 (IL-6) and inducible nitric oxide synthase (iNOS) expressions occurred within 4 to 24 h (9,23,29). It has been found that intravesical NO donors...