ABSTRACT
This study investigated the anti-inflammatory effects of cell-free supernatant of Lactococcus lactis IDCC 2301 on lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. Expression of inflammatory mediators and cytokines, and the production of nitric oxide (NO) and prostaglandin E2 (PGE2) were qualitatively analysed. The expression of signal transductors in inflammatory cascades was quantified by western blot. Treatment with cell-free supernatant of L. lactis IDCC 2301 significantly decreased the mRNA expression levels of tumour necrosis factor (TNF-α) and interleukins including IL-1ß and IL-6. The levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) were also remarkably reduced in LPS-induced macrophages after the treatment. Furthermore, L. lactis IDCC 2301 reduced the levels of both dephosphorylated and phosphorylated forms of nuclear factor-kappa B (NF-κB), IκB-α, extracellular signal-regulated kinases (ERK), c-Jun amino-terminal kinases (JNK), and p38 in LPS-induced RAW 264.7 cells. Therefore, L. lactis IDCC 2301 shows anti-inflammatory activity by suppressing the NF-κB and mitogen-activated protein kinase (MAPK) signaling pathways.
Subject(s)
Anti-Inflammatory Agents , Lactococcus lactis , Lipopolysaccharides , Macrophages , NF-kappa B , Nitric Oxide , Lactococcus lactis/metabolism , Lactococcus lactis/genetics , Animals , Mice , Macrophages/drug effects , Macrophages/immunology , NF-kappa B/metabolism , Anti-Inflammatory Agents/pharmacology , RAW 264.7 Cells , Nitric Oxide/metabolism , Cytokines/metabolism , Cytokines/genetics , MAP Kinase Signaling System/drug effects , Dinoprostone/metabolism , Signal Transduction/drug effects , Cyclooxygenase 2/genetics , Cyclooxygenase 2/metabolism , Nitric Oxide Synthase Type II/genetics , Nitric Oxide Synthase Type II/metabolism , Culture Media, Conditioned/pharmacology , Tumor Necrosis Factor-alpha/metabolism , Tumor Necrosis Factor-alpha/geneticsABSTRACT
Cough variant asthma is an occult form of asthma in which the only sign or symptom is chronic cough. It is a common problem amongst all ages that frequently goes unrecognized, leading to underdiagnosis and undertreatment. To characterize the pathophysiological abnormalities in these patients, we performed bronchial provocation tests with methacholine using the stepwise doubling concentration technique, and measured the concentration of methacholine and the severity of airway obstruction when wheezing was first detected. Airway hyperresponsiveness, defined as PC20 in the cough variant asthma group was not significantly different from that of classic asthma. There was a good correlation between the PCW (the concentration of methacholine causing wheezing) and the PC20 with the PCW values higher than PC20 values in both groups. However, in the cough variant asthma group, the PCW:PC20 ratio was greater than that of the classic asthma group. Furthermore, the mean % fall in FEV1 at which wheezing was first detected in the former group was significantly larger than that of the latter group. The results indicated that the mechanism for the manifestation of cough without wheeze in the cough variant asthma may be a higher wheezing threshold, i.e. wheezing becomes audible at the greater degree of airway obstruction than classic asthma. They suggested that patients with cough variant asthma may represent a subset of asthmatic subjects whose airways are less able to produce a wheeze.
