• 생명과학회지
• /
• 제33권12호
• /
• pp.1062-1073
• /
• 2023

우울증은 개인과 사회에 부정적인 영향을 미치는 흔한 정신질환이지만 그 원인은 아직 명확히 밝혀져 있지 않다. 스트레스는 우울증의 주요 위험인자이며, 염증을 유발하여 우울증에 대한 취약성을 증가시키는 것으로 알려져 있다. 수많은 연구는 우울증과 염증의 강한 연관성을 제안하고 있다. 우울증 환자 혈액에서는 IL-1β, IL-6, IL-12, TNF-α 및 IFN-γ와 같은 친염증성 사이토카인이 증가하였으며, IL-4, IL-10 및 TGF-β와 같은 항염증성 사이토카인이 감소하였다. 설치류에 친염증성 사이토카인을 투여하면 우울 유사 행동이 관찰되는 반면, 항염증제를 투여하면 우울 증상이 완화된다. 이러한 연구들은 우울증의 병인에 염증의 중요성을 강조하고 있다. 우울증에서 염증이 활성화되는 기전에 관한 다양한 연구들이 진행되고 있다. 최근 연구에서는 스트레스로 유발되는 무균 염증의 중요성을 밝히고 있다. 병원균의 감염이 없는 상태에서 신체 및 심리적 스트레스로 인해 염증 과정이 활성화되는 것을 무균 염증이라 한다. 스트레스는 무균 염증을 활성화하기 위해 DAMPs (damage-associated molecular patterns)로 알려진 내인성 인자의 방출을 촉진시키며, 방출된 DAMPs는 해당 수용체인 PRRs (pattern recognition receptors)에 결합함으로서 신호전달을 통해 친염증성 사이토카인 생성을 증가시킨다. 본 종설에서 무균 염증의 조절 장애에 대한 전임상 및 임상 증거를 바탕으로 우울증에서 DAMP의 역할을 검토하고자 한다.

• IMMUNE NETWORK
• /
• 제11권3호
• /
• pp.169-174
• /
• 2011

Background: NADPH oxidase (NOX) modulates cell proliferation, differentiation and immune response through generation of reactive oxygen species. Particularly, NOX2 is recently reported to be important for regulating Treg cell differentiation of CD4+ T cells. Methods: We employed ovalbumin-induced airway inflammation in wild-type and NOX2-deficient mice and analyzed tissue histopathology and cytokine profiles. Results: We investigated whether NOX2-deficiency affects T cell-mediated airway inflammation. Ovalbumin injection which activates T cell-mediated allergic response increased airway inflammation in wild-type mice, as evidenced by increased immune cell infiltration, allergic cytokine expression, and goblet cell hyperplasia in the lung. Interestingly, NOX2 knockout (KO) mice were more susceptible to allergen-induced lung inflammation compared to wild-type mice. Immune cells including neutrophils, lymphocytes, macrophages, and eosinophils were drastically infiltrated into the lung of NOX2 KO mice and mucus secretion was substantially increased in deficiency of NOX2. Furthermore, inflammatory allergic cytokines and eotaxin were significantly elevated in NOX2 KO mice, in accordance with enhanced generation of inflammatory cytokines interleukin-17 and interferon-${\gamma}$ by CD4+ T cells. Conclusion: These results indicate that NOX2 deficiency favorably produces inflammatory cytokines by T cells and thus increases the susceptibility to severe airway inflammation.

• Biomolecules & Therapeutics
• /
• 제26권6호
• /
• pp.539-545
• /
• 2018

4-Hydroxy-2-(4-hydroxyphenethyl)isoindoline-1,3-dione (PD1) is a synthetic phthalimide derivative of a marine compound. PD1 has peroxisome proliferator-activated receptor (PPAR) ${\gamma}$ agonistic and anti-inflammatory effects. This study aimed to investigate the effect of PD1 on allergic asthma using rat basophilic leukemia (RBL)-2H3 mast cells and an ovalbumin (OVA)-induced asthma mouse model. In vitro, PD1 suppressed ${\beta}$-hexosaminidase activity in RBL-2H3 cells. In the OVA-induced allergic asthma mouse model, increased inflammatory cells and elevated Th2 and Th1 cytokine levels were observed in bronchoalveolar lavage fluid (BALF) and lung tissue. PD1 administration decreased the numbers of inflammatory cells, especially eosinophils, and reduced the mRNA and protein levels of the Th2 cytokines including interleukin (IL)-4 and IL-13, in BALF and lung tissue. The severity of inflammation and mucin secretion in the lungs of PD1-treated mice was also less. These findings indicate that PD1 could be a potential compound for anti-allergic therapy.

• The Korean Journal of Pain
• /
• 제12권2호
• /
• pp.171-176
• /
• 1999

Background: Effect of nitric oxide on the hyperalgesia induced by inflammation is controversial. From our previous experiment, NOS inhibitor, L-NAME given during the induction period decrease mechanical hyperalgesia occured by Freund's complete adjuvant induced inflammation. In addition, we attempted to analyze the effects of L-NAME on mechanical hyperalgesia after the development of inflammation by Freund's complete adjuvant in rat paw. Methods: Male Sprague Dawley rats were divided into four groups; control (normal saline), and three different doses of L-NAME (0.1 mg, 1 mg, 10 mg). Inflammation was induced in rats by injecting 0.15 ml of Freund's complete adjuvant (FCA) intraplantarly. Rats showed typical hyperalgesia within twelve hours after injection and maintained this for about one week. Tests were done 2 days after injection of FCA. After the baseline test either L-NAME or saline was injected under light halothane anesthesia. Effect of L-NAME on hyperalgesia was assessed by measuring mechanical hyperalgesia at 15, 30, 60, 90, 120 minutes. Same experients were repeated on normal rats. Results: When injected at the site of inflammation, L-NAME caused dose dependent decrease in mechanical hyperalgesia. However, normal rats also showed increased mechanical threshold after L- NAME injection. Conclusions: Although L-NAME reduces FCA induced mechanical hyperalgesia, this result may solely be due to inhibition of nitric oxide production and need to be further determined.

• The Korean Journal of Physiology and Pharmacology
• /
• 제21권1호
• /
• pp.1-9
• /
• 2017

Intestinal disorders often co-occur with inflammation and dysmotility. However, drugs which simultaneously improve intestinal inflammation and co-occurring dysmotility are rarely reported. Atractylodin, a widely used herbal medicine, is used to treat digestive disorders. The present study was designed to characterize the effects of atractylodin on amelioration of both jejunal inflammation and the co-occurring dysmotility in both constipation-prominent (CP) and diarrhea-prominent (DP) rats. The results indicated that atractylodin reduced proinflammatory cytokines TNF-${\alpha}$, IL-$1{\beta}$, and IL-6 in the plasma and inhibited the expression of inflammatory mediators iNOS and NF-kappa B in jejunal segments in both CP and DP rats. The results indicated that atractylodin exerted stimulatory effects and inhibitory effects on the contractility of jejunal segments isolated from CP and DP rats respectively, showing a contractile-state-dependent regulation. Atractylodin-induced contractile-state-dependent regulation was also observed by using rat jejunal segments in low and high contractile states respectively (5 pairs of low/high contractile states). Atractylodin up-regulated the decreased phosphorylation of 20 kDa myosin light chain, protein contents of myosin light chain kinase (MLCK), and MLCK mRNA expression in jejunal segments of CP rats and down-regulated those increased parameters in DP rats. Taken together, atractylodin alleviated rat jejunal inflammation and exerted contractile-state-dependent regulation on the contractility of jejunal segments isolated from CP and DP rats respectively, suggesting the potential clinical implication for ameliorating intestinal inflammation and co-occurring dysmotility.

• Journal of Nutrition and Health
• /
• 제50권6호
• /
• pp.578-584
• /
• 2017

Purpose: Excess intake of sodium is a major diet-related risk factor for human diseases including hypertension and cancer as well as obesity and inflammation. However, findings are still controversial, and evidence is lacking in Koreans. Therefore, for better understanding of the role of dietary sodium intake in disease etiology, this study investigated the effects of dietary sodium intake on adiposity, inflammation, and hormones in Koreans. Methods: A total of 80 males and females joined the study. The general characteristics and dietary intake data were investigated by trained interviewers using a questionnaire and 24-h dietary recall, respectively. For the markers of adiposity, body weight, body mass index, percent of body fat, visceral fat area, and waist and hip circumference were measured. For the inflammation and hormone markers, leptin, adiponectin, insulin, tumor necrosis $factor-{\alpha}$, and interleukin-6 were also analyzed. Results: Multivariate linear regression analyses suggested that dietary sodium intake was not associated with adiposity. However, dietary sodium showed a significant association with insulin level: Plasma insulin concentration increased with sodium intake independent of other dietary intake or percent of body fat (${\beta}=0.296$, adjusted $r^2=0.276$, p < 0.01). Other markers for inflammation and hormonal responses were not associated with dietary sodium intake. Conclusion: Findings suggested that dietary sodium intake may be a critical modifying factor in the level of plasma insulin. However, it showed a limited effect on obesity and other inflammation markers and hormone levels. These findings should be confirmed in larger, well-designed investigations.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• 제36권1호
• /
• pp.16-22
• /
• 2010

Purpose: The purpose of this study was not only to evaluate the relative mRNA expression of interleukin-$1{\beta}$(IL-$1{\beta}$), cyclooxygenase2 (COX-2) and prostaglandin E2 (PGE2) by RT-PCR analysis but to observe pattern of edema by light microscopic and electron microscope after topical apply of hyaluronic acid in inflammation-guided mouse. Material and methods: Mice of this study were devided into 4 groups: Control group (no inflammation guided), Positive control (inflammation guided + vaselin apply), Protopic group (inflammation guided + protopic apply), Hyaluronic group (inflammation guided + hyaluronic acid apply). Results: Hyaluronic group showed less expressions of IL-$1{\beta}$, COX-2, PGE2 than those of positive control & protopic group. Hyaluronic group revealed a decreased inflammation than positive control & protopic group in Light Microscope. Hyaluronic group appeared decreased edema of ear compare to positive control & protopic group in Elecron Microscope. Conclusion: It was considered that hyaluronic acid has an antiinflammatory effect for intercepting the gene expression of cytokines related to inflammation.

• Journal of Acupuncture Research
• /
• 제34권1호
• /
• pp.23-30
• /
• 2017

Objectives : In this study, the roles of Interleukin (IL)-4 and Signal transducer and activator of transcription 6 (STAT6), which have been reported to play a role in the pathogenesis of inflammation and cancer, were evaluated in snake venom toxin (SVT)-induced apoptosis. Methods : Inflammation was induced in human HaCaT kerationocytes, by lipopolysaccharide (LPS; $1{\mu}g/mL$) or tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), followed by treatment with SVT (0, 1, or $2{\mu}g/mL$). Cell viability was assessed by MTT assays after 24 h, and the expression of levels of IL-4, STAT6, and the apoptosis-related proteins p53, Bax, and Bcl-2 were evaluated by western blotting. Electro mobility shift assays (EMSAs) were performed to evaluate the DNA binding capacity of STAT6. Results : MTT assays showed that inflammation-induced growth of HaCaT cells following LPS or TNF-${\alpha}$ stimulation was inhibited by SVT. Western blot analysis showed that p53 and Bax, which promote apoptosis, were increased, whereas that of Bcl-2, an anti-apoptotic protein, was decreased in a concentration-dependent manner in LPS- or TNF-${\alpha}$-induced HaCaT cells following treatment with SVT. Moreover, following treatment of HaCaT cells with LPS, IL-4 concentrations were increased, and treatment with SVT further increased IL-4 expression in a concentration-dependent manner. Western blotting and EMSAs showed that the phosphorylated form of STAT6 was increased in HaCaT cells in the context of LPS- or TNF-${\alpha}$-induced inflammation in a concentration-dependent manner, concomitant with an increase in the DNA binding activity of STAT6. Conclusion : SVT can effectively promote apoptosis in HaCaT cells in the presence of inflammation through a pathway involving IL-4 and STAT6.

• International Journal of Oral Biology
• /
• 제41권3호
• /
• pp.125-131
• /
• 2016

The aim of the present study was to develop an animal model for evaluation of temporomandibular (TMJ) nociception under TMJ inflammation. We also investigated the participation of $IL-1{\beta}$ in inflammation-induced TMJ nociception. Experiments were carried out using male Sprague-Dawley rats. Intra-articular injection of 3% formalin was administered to evaluate hyperalgesia 3 days after CFA injection. Intra-articular injection of 3% formalin did not produce nociceptive behavior in normal rats. Although intra-articular injection of 3 doses of CFA produced TMJ inflammation, only 1:3 diluted CFA produced hyperalgesia when formalin was injected intra-articularly 3 days after CFA injection. Co-administration of IL-1 receptor inhibitor with formalin into the TMJ cavity 3 days after CFA injection was performed. Co-administration of IL-1 receptor inhibitor significantly inhibited formalin-induced hyperalgesia in rats with CFA-induced TMJ inflammation. These results suggested that intra-articular injection of formalin produced hyperalgesia under chronic TMJ inflammation. Moreover, $IL-1{\beta}$ plays an important role in TMJ hyperalgesia under chronic inflammation and blockade of $IL-1{\beta}$ is a potential therapeutic target for inflammatory TMJ pain.

• Tuberculosis and Respiratory Diseases
• /
• 제78권1호
• /
• pp.8-17
• /
• 2015

Background: AMP-activated protein kinase (AMPK) not only functions as an intracellular energy sensor and regulator, but is also a general sensor of oxidative stress. Furthermore, there is recent evidence that it participates in limiting acute inflammatory reactions, apoptosis and cellular senescence. Thus, it may oppose the development of chronic obstructive pulmonary disease. Methods: To investigate the role of AMPK in cigarette smoke-induced lung inflammation and emphysema we first compared cigarette smoking and polyinosinic-polycytidylic acid [poly(I:C)]-induced lung inflammation and emphysema in $AMPK{\alpha}1$-deficient ($AMPK{\alpha}1$-HT) mice and wild-type mice of the same genetic background. We then investigated the role of AMPK in the induction of interleukin-8 (IL-8) by cigarette smoke extract (CSE) in A549 cells. Results: Cigarette smoking and poly(I:C)-induced lung inflammation and emphysema were elevated in $AMPK{\alpha}1$-HT compared to wild-type mice. CSE increased AMPK activation in a CSE concentration- and time-dependent manner. 5-Aminoimidazole-4-carboxamide-1-${\beta}$-4-ribofuranoside (AICAR), an AMPK activator, decreased CSE-induced IL-8 production while Compound C, an AMPK inhibitor, increased it, as did pretreatment with an $AMPK{\alpha}1$-specific small interfering RNA. Conclusion: $AMPK{\alpha}1$-deficient mice have increased susceptibility to lung inflammation and emphysema when exposed to cigarette smoke, and AMPK appears to reduce lung inflammation and emphysema by lowering IL-8 production.