• The Korean Journal of Physiology and Pharmacology
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• 제27권3호
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• pp.257-265
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• 2023

Kidney ischemia/reperfusion (I/R) injury, a common cause of acute kidney injury (AKI), is associated with the migration of inflammatory cells into the kidney. Ras-related C3 botulinum toxin substrate 1 (Rac1), a member of the Rho family of small GTPase, plays an important role in inflammatory cell migration by cytoskeleton rearrangement. Here, we investigated the role of Rac1 on kidney I/R injury and macrophage migration. Male mice were subjected to either 25 min of bilateral ischemia followed by reperfusion (I/R) or a sham operation. Some mice were administrated with either NSC23766, an inhibitor of Rac1, or 0.9% NaCl (vehicle). Kidney damage and Rac1 activity and expression were measured. The migration and lamellipodia formation of RAW264.7 cells, mouse monocyte/macrophage, induced by monocyte chemoattractant protein-1 (MCP-1, a chemokine) were determined using transwell migration assay and phalloidin staining, respectively. In sham-operated kidneys, Rac1 was expressed in tubular cells and interstitial cells. In I/R-injured kidneys, Rac1 expression was decreased in tubule cells in correlation with the damage of tubular cells, whereas Rac1 expression increased in the interstitium in correlation with an increased population of F4/80 cells, monocytes/macrophages. I/R increased Rac1 activity without changing total Rac1 expression in the whole kidney lysates. NSC23766 administration blocked Rac1 activation and protected the kidney against I/R-induced kidney damage and interstitial F4/80 cell increase. NSC23766 suppressed monocyte MCP-1-induced lamellipodia and filopodia formation and migration of RAW 264.7 cells. These results indicate Rac1 inhibition protects the kidney against I/R via inhibition of monocytes/macrophages migration into the kidney.

• Fisheries and Aquatic Sciences
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• 제6권3호
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• pp.130-134
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• 2003

Proinflammatory effects of bacterial lipopolysaccharide (LPS) have been assessed by analysing the induction of two inflammatory genes, $interleukin-1\beta$ $(IL-1\beta)$ and cyclooxygenase-2 (COX-2), in rainbow trout (Oncorhynchus mykiss) macrophage cells. Production of a metabolite of arachidonic acid by COX-2, prostaglandin $E_2\;(PGE_2)$, was also analysed in macrophage cells after LPS stimulation. Northern blot analysis revealed that LPS $(5{\mu}g/mL)$ significantly upregulated $IL-1\beta$ (54 times) and COX-2 (40.7 times) gene expression in macrophage cells after 4 h stimulation. According to RT-PCR (Reverse Transcription Polymerase Chain Reaction) analysis, $IL-1\beta$ gene induction in LPS stimulated macrophage cells was started within 1h and significantly increased thereafter until 4h. Meanwhile, COX-2 gene induction by LPS was delayed in comparison with $IL-1\beta$ gene induction as a faint band was observed after 4h stimulation in head kidney macrophage cells. LPS also significantly increased $PGE_2$ production in head kidney leucocytes, presumably via activating COX-2 expression that metabolites arachidonic acid to $PGE_2$. In conclusion, it was demonstrated that LPS could induce two main inflammatory and immune related genes, $IL-1\beta$ and COX-2, and increase $PGE_2$ production in trout head kidney macrophage cells, representing a strong inflammatory activity.

• 한국어업기술학회:학술대회논문집
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• 한국어업기술학회 1997년도 수산관련공동학술대회발표요지집
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• pp.291-292
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• 1997

• Clinical and Experimental Pediatrics
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• 제53권7호
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• pp.735-740
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• 2010

Renal fibrosis, characterized by tubulointerstitial fibrosis and glomerulosclerosis, is the final manifestation of chronic kidney disease. Renal fibrosis is characterized by an excessive accumulation and deposition of extracellular matrix components. This pathologic result usually originates from both underlying complicated cellular activities such as epithelial-to-mesenchymal transition, fibroblast activation, monocyte/macrophage infiltration, and cellular apoptosis and the activation of signaling molecules such as transforming growth factor beta and angiotensin II. However, because the pathogenesis of renal fibrosis is extremely complicated and our knowledge regarding this condition is still limited, further studies are needed.

• 한국어병학회지
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• 제14권1호
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• pp.3-10
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• 2001

식물성 생약재의 항균력과 활성산소(superoxide anion, $O_2^-$)의 생산에 미치는 in vitro 효과를 조사하여 금후 in vivo 실험에 적용할 때, 어류 체내 자연 저항성 증진을 꾀할 수 있는 식물성 생약재를 발굴하기 위한 기초자료를 얻고자 하였다. 식물성 생약재는 고삼, 귀전우, 구절초, 박하, 방풍, 연교, 약쑥, 지유, 삼백초, 삼지구엽초, 상백피, 소회향, 편축, 팔각 등 14종류로 이들을 열수추출하여 실험에 사용하였다. 항균력 시험에는 어병세균 Listonella anguillarum(Vibrio anguillarum), Vibrio sp., Vibrio alginolyticus, Edwardsiella tarda, Streptococcus sp., Lactcoccus garvieae를 대상으로 disk법을 사용하였으며, 활성산소의 생산능은 넙치 신장 대식세포를 이용한 nitroblue tetrazolium(NBT) 반응으로써 조사하였다. 그 결과,약쑥이 다른 생약재에 비하여 시험에 사용된 어병 세균에 대한 항균활성이 월등히 뛰어났으며, 또한 넙치 대식세포의 활성산소 생산능을 크게 자극하는 효과가 있음을 확인할 수 있었다.

• 한국어병학회지
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• 제7권2호
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• pp.127-149
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• 1994

경골어류의 비장과 두신에 분포하는 대식세포의 탐식과정 및 탐식활력에 상응한 Melano - Macrophage Centers (MMCs)의 형태학적 변화가 갖는 병리학적 의의를 규명하기 위하여, 어체의 면역활성상태의 변화를 인위적으로 야기한 털라피아, Oreochromis niloticus 에 콜로이드성 탄말을 주입하여 비장 및 두신 MMCs의 병리조직학적 변화에 대한 추이를 경시적으로 추구하였다. 면역활성상태의 변화를 야기할 목적으로 Edwardsiella tarda 유래 formalin killed cell(FKC) 및 lipopolysaccharide (LPS)를 복강내 주사하거나, dexamethasone을 경구투여하였다. 각 처치군에서 모든 틸라피아의 비장 및 두신에 분포하는 대식세포의 탄말탐식유형이나, MMCs와 관련한 탄말탐식세포의 이동상은 유사하였으나, 경시적으로 본 대식세포의 탐식활력과 기존 MMCs 또는 새롭게 형성된 탄말함유세포의 응집유형에 있어서는 무처치군을 포함한 처치군간에 큰 차이를 나타내었다. 무처치군에서는 비장과 두신에 있어 다소 차이는 있으나, 두신의 경우, 탄말투여 12일이 지나서야 MMCs 내의 집적정도가 치밀하였다. 이에 반해 2 가지의 세균유래 항원을 처치한 군에서는 탄말투여 8 일째에 탄말이 기존 MMCs 내로 치밀하게 집적하거나, 탄말함유세포로만 구성된 치밀한 집괴형상을 완료한 반면, dexamethasone 을 처치한 군에서는 8일째 이후에도 탄말을 함유한 세포는 소수만이 관찰되었으며, MMCs 내로의 치밀한 집적이나 탄말함유세포의 집괴는 볼 수 없었다. 본 연구의 결과, 어체의 면역활성상태는 MMCs의 출현수, 크기, 치밀성 및 윤곽에 큰 영향을 미칠 수 있음을 강하게 시사하며, MMCs의 각종 형태학적 소견은 경골어류의 병리조직학적 소견해석에 있어서 도움을 줄 수 있는 중요한 형태학적 증거가 될 수 있는 것으로 사료된다.

• Fisheries and Aquatic Sciences
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• 제12권1호
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• pp.49-53
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• 2009

We conducted a histological analysis to investigate the influence of nutritional changes on melano-macrophages (MMs) accumulation in the kidney of sub-adult rock bream (Oplegnathus fasciatus). Four experimental groups were established (initial control, control, fed and starved), and fed commercial feed amounting to 1-3% of their body weight for 2 weeks prior to initiation of experiments. Kidney MMs with dark brown pigment were randomly observed in the kidneys of starved fish, increasing rapidly after 4 weeks, while deposition levels remained low throughout the experiment in the control and fed groups. These results suggest that catabolic tissue breakdown is a major factor contributing to the formation of pigments within MMs. Results also suggest that the degree of MMs deposition in the kidney can be used as alternative indicators in identifying starvation in wild and cultured rock bream.

• 동의생리병리학회지
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• 제21권2호
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• pp.491-497
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• 2007

Hyeonggaeyeongyo-tang (HYT; Jingjielianqiao-tang), is known to be effective in lowering wind-heat blended as a pathogen of kidney. HYT has been traditionally used for the treatment of a syndrome in kidney meridian, due to invasion of pathogenic wind and heat. Nowadays, this prescription is used to treat diseases marked by excessive wind and heat in the kidney meridian, such as acute otitis media, empyema, hypertrophic rhinitis, nasal bleeding, nasal obstruction, acne and tonsillitis. The present study was conducted to evaluate the effect of HYT on the regulatory mechanism of cytokines and nitric oxide (NO) for the immunological activities in Raw 264.7 cells. After the treatment of HYT water extract, cell viability was measured by MTT assay, NO production was monitored by measuring the nitrite content in culture medium. Cyclooxygenase-2 (COX-2_ and inducible nitric oxide synthase (iNOS) were determined by immunoblot analysis, and levels of cytokine were analyzed by sandwich immunoassays. The production of No was significantly inhibited by pre-treatment (1h) with HYT(0.1-0.3 mg/ml) on LPS-activated Raw264.7 cells. The expression of iNOS and COX-2 protein were up-regulated by LPS, but the increased levels of iNOS and COX-2 were inhibited by pre-treatment of HYT (0.3-1.0 mg/ml), respectively. And the level of interleukin-6 (IL-6), cytokine released from macrophage, was reduced by HYT pre-treatment (0.3-1.0 mg/ml). Thus, the present data suggest that HYT may play an important role in adjunctive therapy in Gram-negative bacterial infections.

• The Korean Journal of Physiology and Pharmacology
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• 제25권2호
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• pp.139-146
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• 2021

Mitochondrial NADP+-dependent isocitrate dehydrogenase 2 (IDH2) produces NADPH, which is known to inhibit mitochondrial oxidative stress. Ureteral obstruction induces kidney inflammation and fibrosis via oxidative stress. Here, we investigated the role and underlying mechanism of IDH2 in unilateral ureteral obstruction (UUO)-induced kidney inflammation using IDH2 gene deleted mice (IDH2-/-). Eight- to 10-week-old female IDH2-/- mice and wild type (IDH2+/+) littermates were subjected to UUO and kidneys were harvested 5 days after UUO. IDH2 was not detected in the kidneys of IDH2-/- mice, while UUO decreased IDH2 in IDH2+/+ mice. UUO increased the expressions of markers of oxidative stress in both IDH2+/+ and IDH2-/- mice, and these changes were greater in IDH2-/- mice compared to IDH2+/+ mice. Bone marrow-derived macrophages of IDH2-/- mice showed a more migrating phenotype with greater ruffle formation and Rac1 distribution than that of IDH2+/+ mice. Correspondently, UUO-induced infiltration of monocytes/macrophages was greater in IDH2-/- mice compared to IDH2+/+ mice. Taken together, these data demonstrate that IDH2 plays a protective role against UUO-induced inflammation through inhibition of oxidative stress and macrophage infiltration.

• The Korean Journal of Physiology and Pharmacology
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• 제6권3호
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• pp.155-160
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• 2002

It is not known whether gender differences play a role in susceptibility to ischemic acute renal failure. Thus, we examined if there were any differences in susceptibility between male and female mice to kidney ischemic injury, and if so, whether it is due to differences in mitogen activated protein kinases (MAPKs) or inflammatory responses to ischemia. Female mice were protected against kidney ischemia when compared with males. Thirty minutes of bilateral ischemia resulted in marked functional and morphological damages in males, but not in females. The ischemia-induced phosphorylation of c-jun N-terminal stress-activated protein kinases (JNKs) was higher in males than in females. Phosphorylation of extracellular signal-regulated kinases (ERKs) was lower in males than in females. Post- ischemia medullary infiltration of RAW 264.7 cell, a monocyte-macrophage cell, and intercellular adhesion molecule-1 (ICAM-1) were greater in males than in females. In conclusion, males were much more susceptible to ischemia than females. The enhanced propensity to ischemic injury in males was correlated with greater activation of JNKs, greater expression of ICAM-1, and greater trapping of leukocytes in the medulla.