[65], [66], [67], [68], [69], [70], [71], [72], [73], [74], [75], [76] and [77] “
“The pungent component of capsicum, capsaicin (Cap), has several associated physiological activities, including anti-oxidant, anti-bacterial and anti-inflammatory effects [5], [13] and [15]. LPS

is an outer membrane component of Gram-negative bacteria and has been reported to activate NF-κB via toll-like receptor 4 (TLR4), which is present on antigen-presenting cells such as dendritic cells or macrophages [6], releasing pro-inflammatory mediators, including TNF-α, interleukins (IL-1β, IL-6, IL-10), [12] and [28], and nitric oxide (NO), [19]. Macrophages can also release TNF-α (as soluble TNF [sTNF]) [16], which mediates its biological activities through binding to type 1 and 2 TNF receptors (TNF-R1 RGFP966 solubility dmso and -R2) [10] and [18]. In addition, TNF-R2, the principal mediator of the effects of TNF-α on cellular immunity, may cooperate with TNF-R1 in the killing of nonlymphoid cells [1]. When TNF-R1 and/or -R2 are stimulated by TNF-α, the extracellular portions of transmembrane proteins are cleaved,

soluble ectodomains are released from the cell surface by a sheddase known as TNF-converting enzyme (TACE) [29], and sTNF is neutralized by the sTNF-Rs [21]. After cell stimulation by BIRB 796 concentration various stimuli, including TNF-α itself, these two receptors can be proteolytically cleaved by TACE [17] into many two soluble forms, sTNF-R1 and sTNF-R2, which show prolonged elevation in the circulation of patients with various inflammatory diseases such as septicemia, leukemia, hepatitis C virus infection, lupus, rheumatoid arthritis, and congestive heart failure [2], [3], [8], [14], [20], [22], [23] and [26]. Furthermore, increased circulating levels of sTNF-R1 and -2 have been reported in a rat model of CCL4 induced-liver injury [11]. The aim of this

study was to investigate the effect of Cap on circulating TNF-α (sTNF), sTNF-R1, and -R2 levels in LPS-treated mice. The expression of TNF-α, sTNF-R1 and -R2 proteins and mRNA were also examined in blood at different time points. LPS (Escherichia coli, 055:B55, Lot No. 114K4107) was purchased from Sigma-Aldrich, Co. (MO, USA), and Cap (98% purity) was provided by Maruishi Pharmaceutical Co., Ltd. (Osaka, Japan). Other reagents used were commercially available extra-pure grade chemicals. Male BALB/c mice (age, 8-10 weeks; weight, 21–26 g; Japan SLC, Inc., Shizuoka, Japan) were used. They were housed for at least one week under controlled environmental conditions (temperature, 24 ± 1 °C; humidity, 55 ± 10%; light cycle, 6:00–18:00) with free access to solid food (NMF, Oriental yeast Co., Ltd., Tokyo, Japan) and water. All experimental procedures were conducted according to the guidelines for the use of experimental animals and animal facilities established by Osaka University of Pharmaceutical Sciences.