IL-1RAcP는 일명 interleukin-1 receptor accessory protein이라 칭하며 interleukin-1 염증성 사이 토카인과 interleukin-1 receptor I (IL-1RI) 결합체와 복합체를 형성하여 작용한다. IL-1RAcP는 면 역반응, 스트레스 및 세포사멸과 관련이 있다. 본 연구의 목적은 참돔(Pagrus major)을 저수온 (8℃, 33 psu) 및 저염분(20℃, 10 psu) 상태에 노출시킨 후, IL-1RAcP 유전자의 발현을 관찰하는 것이다. 연구결과, IL-1RAcP 유전자의 발현은 저수온(8℃, 33 psu) 및 저염분(20℃, 10 psu) 상태 에서 유의적으로 증가하는 것으로 나타났다. 이 연구결과로서 IL-1RAcP 유전자는 저수온 및 저 염분 등의 환경 스트레스에 대한 생체지표유전자로서 역할을 한다고 제의한다.

Sulfated polysaccharides are known to be immune-stimulators in mammals and can be used as food additives to enhance immunity. In this study, the immune-stimulating activity of water-soluble anionic macromolecules F2 fractionation isolated from Codium fragile using ion-exchange chromatography was tested in olive flounder, Paralichythys olivaceus, in vitro and in vivo. The gene expression of interleukin (IL)-1β was adopted to check the immune-affection. As a result, in vitro study revealed that the expression of IL-1β was significantly upregulated in head kidney cells by 1 and 5 μg/ml of polysaccharides 4 h and by 5 μg/ml of polysaccharides at 24 h. In vivo, IL-1β gene expression in head kidney was significantly upregulated by 20 and 100 μg of the polysaccharides at day 1 post-i.p. injection, while downregulated at day 3 but not significant. Meanwhile, in peritoneal cells, it was upregulated by 20 μg of the polysaccharides at day 1 but the upregulation was sustained until day 3 though it was not significant. These results indicate that the sulfated polysaccharides from C. fragile are an immune-stimulator and might be potential feed additives for olive flounder.

Inflammation mainly mediated by innate immune cells as the first line of host defense against pathogens is an acute response that limits tissue damage and eliminates pathogens in the body. In triggering inflammation, several pattern recognition receptors work together; membrane-associated Toll-like receptors, c-type lectin receptors, retinoic acid-inducible gene-like helicase receptors, absent in melanoma-like receptors, and cytosolic nucleotide-binding domain and leucine-rich repeat receptors. Among them, inflammasome is a newly trigger of inflammation in response to exogenous and endogenous stimuli and its activation leads to the assembly of multiprotein platforms composed of NLRP3 (NOD-like receptor family, pyrin domain containing 3), ASC (apoptosis associated speck-like protein containing a CARD), and procaspase 1. Thus, the activated inflammasome activates caspase 1, resulting in processing and secretion of interleukin (IL)-1β. Recent emerging data suggest that dysregulated metabolites, i.e., amyloids, ceramides, and cholesterol crystals, have been classified as inflammasome activators. In addition, IL-1β may play a critical role in the pathogenesis of chronic inflammation-induced disorders such as Alzheimer’s diseases, type 2 diabetes, and atheriosclerosis. This review introduces the basic concept of inflammasome activation and auto-inflammatory diseases. In addition, it discusses the updated signaling models of inflammasome activation that link metabolic dysfunction in order to outline future therapeutic approaches to inflammasome-mediating diseases.

Aggregatibacter actinomycetemcomitans is the most important etiologic agent of aggressive periodontitis and can interact with endothelial cells. Monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) are chemokines, playing important roles in periodontal pathogenesis. In our current study, the effects of A. actinomycetemcomitans on the production of MCP-1 and IL-8 by human umbilical vein endothelial cells (HUVEC) were investigated. A. actinomycetemcomitans strongly induced the gene expression and protein release of both MCP-1 and IL-8 in a dose- and time-dependent manner. Dead A. actinomycetemcomitans cells were as effective as live bacteria in this induction. Treatment of HUVEC with cytochalasin D, an inhibitor of endocytosis, did not affect the mRNA up-regulation of MCP-1 and IL-8 by A. actinomycetemcomitans. However, genistein, an inhibitor of protein tyrosine kinases, substantially inhibited the MCP-1 and IL-8 production by A. actinomycetemcomitans, whereas pharmacological inhibition of each of three members of mitogen-activated protein (MAP) kinase family had little effect. Furthermore, gel shift assays showed that A. actinomycetemcomitans induces a biphasic activation (early at 1-2 h and late at 8-16 h) of nuclear factor-κB (NF-κB) and an early brief activation (0.5-2 h) of activator protein-1 (AP-1). Activation of canonical NF-κB pathway (IκB kinase activation and IκB-α degradation) was also demonstrated in these experiments. Although lipopolysaccharide from A. actinomycetemcomitans also induced NF-κB activation, this activation profile over time differed from that of live A. actinomycetemcomitans. These results suggest that the expression of MCP-1 and IL-8 is potently increased by A. actinomycetemcomitans in endothelial cells, and that the viability of A. actinomycetemcomitans and bacterial internalization are not required for this effect, whereas the activation of protein tyrosine kinase(s), NF-κB, and AP-1 appears to play important roles. The secretion of high levels of MCP-1 and IL-8 resulting from interactions of A. actinomycetemcomitans with endothelial cells may thus contribute to the pathogenesis of aggressive periodontitis.

The purpose of the present study was to examine the role of peripheral nitric oxide (NO) pathways in the onset of interleukin (IL)-1β-induced mechanical allodynia in the orofacial area. Experiments were carried out on male Sprague-Dawley rats weighing 230-280 gm and surgical procedures were performed under pentobarbital sodium (40 mg/kg, i.p.). Under anesthesia, a polyethylene tube (PE10) was implanted into the subcutaneous area of one vibrissa pad, which enabled the injection of IL-1β or other chemicals. We subcutaneously injected 50 μL of IL-1β into a vibrissa pad through the implanted polyethylene tube with a 100 Hamilton syringe. After the administration of 0.01, 0.1, 1, or 10 pg of IL-1β, withdrawal behavioral responses were examined. The subcutaneous injection of saline had no effects on the air-puff thresholds. Following the subcutaneous injection of 0.01, 0.1, 1, or 10 pg of IL-1, the threshold of air puffs decreased significantly to 12± 3, 7 ± 2, 5 ±1, or 5 ± 1 psi, respectively, in a dose dependent manner. Pretreatment with L-NAME, a nitric oxide synthase (NOS) inhibitor, blocked IL-1β-induced mechanical allodynia. However, neither D-NAME, an inactive isomer of L-NAME, nor vehicle affected the IL-1β-induced mechanical allodynia. Subcutaneous injection of IL-1 increased the number of c-fos-like immunoreactive neurons, whereas pretreatment with L-NAME decreased this number, in the trigeminal caudal nucleus. These results suggest that pro-inflammatory cytokines and NO are important contributors to the pathogenesis of persistent and exaggerated IL-1β-induced pain states. Based on these observations, peripheral application of NOS inhibitors may be of therapeutic value in treating pain disorders in the clinic.

Nitric oxide(NO) is a labile, uncharged, reactive radical that functions as a sensitive mediator of intercellular communication in diverse tissues. It has been reported that NO is produced by osteoblast and these results may suggest that NO is integrally involved in the regulation of osteoclast formation and osteoclast resorption activity by osteoblastic cells. We examined the effect of cytokines on NO release by mouse bone marrow cell. We also examined the effects of cytokines and sodium nitroprusside(SNP) on the formation of osteoclast-like cell from mouse bone marrow cells in culture. Cytokines stimulated NO production of mouse bone marrow cells, and N-nitro-L-arginine methyl ester, a specific inhibitor of NO synthase, suppressed the cytokine-induced NO production. SNP showed dual action in the generation of osteoclasts. The addition of (30μM)SNP inhibited the formation of tartrate resistant acid phosphatase(TRAP)(+) multinucleated cell, whereas lower concentration(30μM) of SNP enhanced it. Although the precise action of NO remains to be elucidated in detail, the action of NO in osteoclast generation in our studies seems to be associated, at least in part, with bone metabolism and bone pathophysiology.

In odontogenic osteolytic lesions, the mechanism involved in inflammation 때d osteolysis is still under debate. We investigated the role 。OL-l ~ -1 ß, -4, -6, -8, TNF- a in the expansion of the odontogenic cysts, by using 50 cases of excised odontogenic cysts. The degrees of inflammation were graded into 2 groups and immunohistochernical stainings were performed, The cytoplasrnic reaction in squamous epithelial cells, stromal cells and infIitrating inflammatory cells was examined. The relationship between the expressions of IL-1 q -1 ß, -4, -6, -8, π-JF- aand the degree of inflammation and the correlation among them were analyzed. 까1e 비Stilαγtic expressions of IL-l ~ IL-l ß and TNF-awere 66.6%, 66.6% and 4O.00Al respeαively and the epithelial exp~않sions of IL-4, -6, -8 were 32.00Al, 38.00Al and 24.00Al respeαively. IL-4, -6 and 용 were positively stained in plasma cells in 38.00Al, endothelial cells in 40.00/0 and neutrophils in 24. 00Al respectively. The expresssion rate of IL-4 in plasma cells and IL-8 in epithelium and neutrophils were inα얹sed in ca않s with marked inflammation. 까1e exp!1않sion rate of IL-1 ßin 피해ocytes and IL-4 in plasma cells were positively correlated with the expæssion of TNF-1 ain histiocytes. π1e expression rate of anti-inflammatory cytokine IL-4 in the epithelium were correlated with the expression of IL-6 in the epithelium and endothelial cells. A1though statistically insi.맑표ìcant， the expression rate of IL-6 were decreased in cases with marked inflammation and nega디vely correlated with IL-8, the proinflammatory cytokine, and the expressions of IL-4 and IL-6 in the epithelium can be considered as inhibiting the inflammatory reaction. These results suggest that the expressions of IL-4 and IL-6 suppress and IL-8 stimulates the inflammatory reaction in Odontogenic Cysts.

This study aimed to investigate changes in the activity and mRNA expression of plasminogen activators (PAs) induced by 17β-estradiol (E₂), human chorionic gonadotropin (hCG), and interleukin-1β (IL-1β) in porcine endometrial cells. Endometrial cells were isolated from the epithelium and cultured to 80% confluence. They were then treated for 24 h with E₂ (0.2, 2, 20, and 200 ng/mL), IL-1β (0.1, 1, 10, and 100 ng/mL), and hCG (0.5, 1, 1.5 and 2 IU/mL). mRNA expressions of urokinase-type (uPA) and tissue-type (tPA) PAs were analyzed using reverse transcription PCR, and activities were measured using a PA activity assay. mRNA expressions of uPA and tPA increased with E₂ treatment; however, this was not significant. Similarly, treatment with hCG did not influence the mRNA expressions of PAs. Interestingly, treatment with 0.1 ng/mL IL-1β significantly reduced the mRNA expression of uPA, but did not affect that of tPA. Treatment with 2, 20, and 200 ng/mL E₂ increased PA activity compared with the control group; treatment with 0.1 and 1 ng/mL IL-1β significantly increased PA activity compared with the other IL-1β treatment groups, whereas treatment with 10 and 100 ng/mL IL-1β decreased. Treatment with 2 IU/mL hCG increased PA activity compared with the other treatment groups, although there were no significant differences between the hCG and control groups. In conclusion, the activity and mRNA expression of PAs were differently regulat-ed by the hormone/cytokine and its concentration in porcine endometrial cells. Therefore, understanding PA regulatory mechanisms may help to improve the reproductive potential of domestic animals.

Interleukin(IL)은 cytokines의 group으로 주로 macrophages에 의해 생산되어지며, 그 중 IL-1 system 은 염증반응과 면역 및 항상성을 조절한다. Interleukin-1은 Interleukin-1α(IL-1α)와 Interleukin-1β (IL-1β) 2개의 isoform이 존재하며, 이는 IL-1Receptor1(IL-1R1)과 IL-1Receptor2(IL-1R2) 두 가지 타입의 receptor에 결합하여 작용한다. 또한 IL-1R1의 신호전달에는 IL-1 receptor accessory protein (IL-1RAcP)가 필요로 한다. 또한 IL-1RAcP와 IL-1R1은 Toll interacting protein(TOLLIP)과도 작용한 다고 알려져 있다. Interleukin-1 cytokine family member 중 Interleukin-1 receptor antagonist(IL-1Ra)는 IL-1α와 IL-1β의 작용을 저해한다. 선행된 다른 연구에서는 IL-1의 과발현이 정자형성에 대한 부정 적인 효과를 주는 것이 밝혀진바 있다. 따라서 본 연구에서는 정자에서 IL-1α, IL-1β, IL-1R1, IL-1RAcP와 TOLLIP의 발현 여부와 IL-1α, IL-1β와 IL-1Ra가 정자에 미치는 영향을 알아보고자 하였으며, 정자에게 미치는 영향 중에서도 정자의 운동성에 관여한다고 알려져 있는 GSK3의 억제성 인산화 형태인 p-GSK3에 대해서 알아보고자 하였다. 실험 결과, 생쥐의 정자에서 IL-1α, IL-1β, IL-1R1, IL-1RAcP와 TOLLIP이 모두 정자에서 발현되는 것을 확인하였다. Western blot 실험 결과, IL-1α, IL-1β가 단독 처리된 생쥐 정자에서 p-GSK3의 발현이 증가한 것을 확인하였다. 그리고 IL-1Ra가 처리된 경우 p-GSK3의 발현이 생쥐 정자에서 대조군에 비해 감소한 것을 확인하였다. IL-1 α, IL-1β를 IL-1Ra와 함께 처리 시에는 IL-1α, IL-1β를 단독처리 했을때 보다 생쥐의 정자에서 p-GSK3의 발현이 감소한 것을 확인하였다. 이러한 결과를 토대로 IL-1과 IL-1R1이 정자에서 발현되며, IL-1 및 IL-1Ra 처리시 p-GSK3의 발현에 영향을 미치는 것으로 보아 IL-1이 정자운동성에도 관여하는 것으로 사료된다.