Role of proinflammatory cytokines in cisplatin-induced vestibular hair cell damage

Kim, Hyung-Jin,So, Hong-Seob,Lee, Jeong-Han,Park, Channy,Lee, Jin-Bin,Youn, Myung-Ja,Kim, Se-Jin,Yang, Sei-Hoon,Lee, Kang-Min,Kwon, Kang-Beom,Park, Byung-Hyun,Park, Raekil Wiley Subscription Services, Inc., A Wiley Company 2008 Head & neck Vol.30 No.11

<B>Background.</B><P>Cisplatin causes the impairment of inner ear functions, including hearing and balance, through the involvement of a number of mechanisms. However, no laboratory studies have been performed on involvement of inflammation-related events in cisplatin-mediated vestibular dysfunction.</P><B>Methods.</B><P>We evaluated the secretion of proinflammatory cytokines and nuclear factor-κB (NF-κB) activation in cisplatin-treated UB/UE-1 utricular epithelial cells. We also employed immunohistochemistry to detect proinflammatory cytokines and NF-κB expression in cisplatin-injected mice.</P><B>Results.</B><P>Productions of proinflammatory cytokines significantly caused the death of UB/UE1 cells by cisplatin. Pharmacologic inhibition of mitogen-activated protein (MAP) kinase/ERK kinase-1 (MEK1) or extracellular signal-regulated kinase (ERK) significantly attenuated the death of UB/UE1 cells caused by cisplatin and proinflammatory cytokines. Immunohistochemical studies revealed an increase in the expression of proinflammatory cytokines and NF-κB in both the cristae ampullae and utricle of cisplatin-injected mice.</P><B>Conclusions.</B><P>These results suggest that proinflammatory cytokines may play an important role in the pathogenesis of cisplatin-mediated vestibulotoxicity. © 2008 Wiley Periodicals, Inc. Head Neck, 2008</P>

전염증성 사이토카인에 의해 유도된 베타세포 자연사에 대한 유비퀴틴화를 통한 GLP-1의 보호효과

임동미,김주영,이강우,박근용,김병준 대한내분비학회 2011 Endocrinology and metabolism Vol.26 No.2

Background: Proinflammatory cytokines are one of the causes of diabetes mellitus. However, the exact molecular mechanism by which proinflammatory cytokines induce β-cell death remains to be clearly elucidated. Glucagon-like peptide-1 (GLP-1) affects the stimulation of insulin secretion and the preservation of β-cells. Additionally, it may exert an antiapoptotic effect on β cells; however,the mechanism underlying this effect has yet to be demonstrated. Therefore, we investigated the protective effects of GLP-1 in endoplasmic reticulum (ER)-mediated β-cell apoptosis using proinflammatory cytokines. Methods: To induce ER stress, hamster insulin-secreting tumor (HIT)-T15 cells were treated using a mixture of cytokines. Apoptosis was evaluated via MTT assay, Hoechst 33342 staining, and annexin/propidium iodide (PI) flow cytometry. The mRNA and protein expression levels of ER stress-related molecules were determined via PCR and Western blotting, respectively. Nitric oxide was measured with Griess reagent. The levels of inducible nitric oxide synthase (iNOS) mRNA and protein were analyzed via real-time PCR and Western blot, respectively. iNOS protein degradation was evaluated via immunoprecipitation. We pretreated HIT-T15 cells with exendin (Ex)-4 for 1 hour prior to the induction of stress. Results: We determined that Ex-4 exerted a protective effect through nitric oxide and the modulation of ER stress-related molecules (glucose-regulated protein [GRP]78, GRP94, and CCAAT/enhancer-binding protein homologous protein [CHOP]) and that Ex-4stimulates iNOS protein degradation via the ubiquitination pathway. Additionally, Ex-4 also induced the recovery of insulin2 mRNA expression in β cells. Conclusion: The results of this study indicate that GLP-1 may protect β cells against apoptosis through the ubiquitination pathway.

Ketamine reduces the induced spinal p38 MAPK and pro-inflammatory cytokines in a neuropathic rats

권소영,염제화,주진덕 대한마취통증의학회 2014 Korean Journal of Anesthesiology Vol.66 No.1

Background: Neuropathic rats created by spinal nerve ligation are known to show higher levels of p38, c-Jun NH2-terminal kinase, and extracellular signal-regulated kinase p44/42 (ERK 1/2) of the mitogen-activated protein kinases (MAPKs). The authors of this study aimed to understand the effect of ketamine on p38 MAPK and inflammatory responses, as well as its effect on the development of neuropathic pain. Methods: The neuropathic rats were prepared by Chung's method with Sprague-Dawley rats. The research was carried out on three groups, a sham-operated group, a neuropathic pain and normal saline (NP + NS) group, and a neuropathic pain and ketamine (NP + Keta) group. The normal saline or ketamine was infused into the neuropathic rats through a mini-osmotic pump implanted in the subcutaneous space. After a week, the quantities of phospho-p38, p38 MAPK and pro-inflammatory cytokines were measured and compared through western blots and reverse transcriptase-polymerase chain reaction. Results: In comparison to the control group, the NP + NS group showed a significant increase of phospho-p38 and p38 MAPK, as well as of the proinflammatory cytokines, tumor necrosis factor α (TNFα), and intercellular adhesion molecule 1 (ICAM1). However, in the NP + Keta group, phospho-p38, p38 MAPK and TNFα and, ICAM1 were reduced in comparison to the NP + NS group. The paw withdrawal threshold test also showed the trend of recovery from the mechanical allodynia in the NP + Keta group. Conclusions: In the development of neuropathic pain, p38 MAPK and inflammatory responses are significantly related, and the use of ketamine reduces p38 MAPK and proinflammatory cytokines. Thus, the adequate use of ketamine could be effective for the prevention and treatment of neuropathic pain following peripheral injury.

PM(10)이 A549 Cells에서 전염증성 Cytokine발현에 미치는 영향

김정호 ( Jung Ho Kim ),전효근 ( Hyo Keun Jeon ),김미경 ( Mi Kyeong Kim ),경선영 ( Sun Yong Kyung ),안창혁 ( Chang Hyeok An ),이상표 ( Sang Pyo Lee ),박정웅 ( Jung Woong Park ),정성환 ( Sung Hwan Jeong ) 대한결핵 및 호흡기학회 2006 Tuberculosis and Respiratory Diseases Vol.60 No.6

연구배경: 미세먼지는 여러 가지 유기물과 무기물의 복합체로 그 구성 성분이 시간과 장소에 따라 다르고 모양과 크기도 일정하지 않으며, 특히 지름 10㎛이하의 미세먼지 (particulate matter 10; PM(10))는 흡입이 가능한 입자의 크기여서 하부기관지 및 폐의 가스-교환부분까지 침착하여 호흡기계에 손상을 일으킬 수 있다. 본 연구에서는 황사에 포함된 PM(10)과 비황사 시기에 포집된 PM(10)이 폐상피세포주에 작용하여 전염증성 사이토카인(proinflammatory cytokine) 및 cytokine messenger RNA(mRNA)의 발현에 어떤 영향이 있는지를 관찰하여 기관지 천식과 만성 폐쇄성 폐질환등 호흡기 질환의 증상 악화기전에 미치는 역할을 규명하고자 하였다. 연구방법: 공기 포집기(HV 500F, sibata model)를 이용하여 황사와 비황사 기간에 하루 6시간씩 실외의 장소에서 대기분진을 membrane filter에 포집한 다음, PM(10)입자를 추출하고 폐암 상피세포주인 A549 cells(한국세포은행주)에 PM(10)을 농도에 맞게(10㎍/㎖, 100㎍/㎖, 500㎍/㎖) 노출시켰다. 각각의 노출된 세포로부터 interleukin(IL)-1α, IL-1β, IL-8, granulocyte macrophage colony stimulating factor(GM-CSF)의 mRNA를 역전사중합효소연쇄반응(reverse transcriptase polymerase chain reaction; RT-PCR) 방법으로 측정하였다. 결과: 황사 및 비황사 기간 중 포집된 PM10을 가했을 시 가하지 않은 대조군에 비하여 IL-1α, IL-1β, IL-8, granulocyte macrophage colony stimulating factor (GM-CSF)의 m`RNA와 cytokine의 발현이 유의하게 높았으며, 황사 기간의 고농도의 PM(10)에 노출된 세포의 IL-1α mRNA는 비황사 기간의 PM(10)에 노출된 세포의 mRNA보다 증가되어 있었다. 결론: PM(10)은 A549 cells에서 전염증성 사이토카인의 발현을 증가시키고 비황사 기간보다 황사 기간 중 대기 중에서 채취한 PM(10)에 노출된 A549 cells에서 일부의 전염증성 사이토카인의 mRNA발현을 더욱 증가시키는 것을 알 수 있었다. 따라서 황사 기간의 PM(10)에 의한 일부의 전염증성 사이토카인의 발현 증가가 만성 호흡기 질환의 증상 악화기전에 연관되어 있을 가능성을 시사하였다. Background: PM(10)(Particulate matter with a diameter < 10㎛), which is characterized by different environmental conditions, is a complex mixture of organic and inorganic compounds. The Asian dust event caused by meteorological phenomena can also produce unique particulate matter in affected areas. This study investigated the cytokine produced by A549 epithelial cells exposed to particles collected during both the Asian dust pfenomenon and ambient air particles in a non-dusty period. Method: Air samples were collected using a high volume air sampler(Sibata Model HV500F) with an air flow at 500ℓ/min for at least 6 hours. The cytokine messenger RNA(mRNA) was measured using a reverse transcriptase polymerase chain reaction(RT-PCR). The A549 cells were exposed to 10 to 500㎍/㎖ of a suspension containing PM(10) for 24 hours. Each was compared with those in the non-exposed control cells. Result: The mRNA levels of interleukin(IL)-1α, IL-Iβ , IL-8, and the granulocyte macrophage colony stimulating factor(GM-CSF) increased after veing exposed to PM(10) in the ambient air particles, compared with those in the non-exposed control cells. The increase in IL-1α and IL-8 were dose dependent at a PM(10) concentration between 100㎍/㎖ and 500㎍/㎖. The mRNA level of IL-8 in the A549 epithelial cells was higher during the in the Asian dust period(500㎍/㎖) than during the non dust period. Conclusion: A549 cells exposed to the PM(10) collected during the Asian dust period produce more proinflammatory cytokine than during non-dusty period. This cytokine enhances the local inflammatory response in the airways and can also contribute to the systemic component of this inflammatory process. (Tuberc Respir Dis 2006; 60: 663-672)

Inhibition of Proinflammatory Cytokine-induced Invasiveness of HT-29 Cells by Chitosan Oligosaccharide

( Kyung Soo Nam ),( Mee Kyung Kim ),( Yun Hee Shon ) 한국미생물생명공학회 2007 Journal of microbiology and biotechnology Vol.17 No.12

측두하악장애환자에서 악관절 세척술후 관절활액의 전구염증성 Cytokines의 발현

김철훈(Cheol-Hun Kim),황희성(Hie-Sung Hwang),신상훈(Sang-Hoon Shin),정인교(In-Kyo Chung),황태호(Tae-Ho Hwang) 대한구강악안면외과학회 2005 대한구강악안면외과학회지 Vol.31 No.5

The purpose of this study is that evaluate the distribution and biological roles of TNF-a, interleukin-1β(IL-1β), interleukin-6(IL-6) and tissue inhibitors of metalloproteinase-1(TIMP-1) in the synovial fliud of patients with non-inflammatory chronic temporomandibular joint(TMJ) disorders in relation to pain during joint movements and magnetic resonance imaging(MRI) findings. TMJ synovial fluids aspirates were obtained from 36 patients (36 joints) with chronic TMJ disorders and from 8 controls(8 joints). Patients were divided to four groups. The control group was from healthy volunteers(8 joints), group I(18 joints) was patients with anterior disc displacement with reduction, group II(5 joints) was patients with disc displacement without reduction and group III (5 joints) was osteoarthritis. The TNF-α, IL-1βand IL-6 levels in the aspirates were determined by using an enzyme-linked immunosorbent assay and the TIMP-1 level was measured by an enzyme immunoassay. Following examinations for pain during joint movements and MRI observations, these cytokines’level and frequencies of detection were compared. The level of IL-1βwas not significant different in all groups. but the level of TNF-α, IL-6 and TIMP-1 were significant different among groups. The level of IL-6 and TIMP-1 were correlated to pain during movement(p〈0.01) and the level of TNF-a(p〈0.05). Also, the level of IL-6 was correlated to the level of TIMP-1(p〈0.01). Especially, The level of the TIMP-1 level was significantly correlated to the pain during movement and showed very high levle of Pearson’s correlation coefficient (r=0.833)(p〈0.001). The results indicated that the TNF-α, IL-6 and TIMP-1 levels in the TMJ aspirates of patients with chronic TMJ disorders have been raised. Especially, IL-6 and TIMP-1 were very high levels in the patients who were degraded in the TMJ. Also, TNF-α, IL-6 and TIMP-1 showed the significant correlation in the chronic temporomandibular joint disorders. Therefore I suggest that these cytokines were also correlated to the pain during movement in the chronic temporomandibular joint disorders

Inflammatory Bowel Disease and Cytokine

Eun Young Choi(최은영),Kwang Keun Cho(조광근),In Soon Choi(최인순) 한국생명과학회 2013 생명과학회지 Vol.23 No.3

크론병과 궤양성 대장염으로 잘 알려져 있는 염증성 장질환은 재발과 호전을 반복하는 만성적인 염증 및 이에따른 합병증을 특징으로 하는 원인 불명의 질환이다. 염증성 장질환의 발생 원인은 아직 명확히 알려져 있지 않지만 흡연이나 식이와 같은 환경적 요인, 장내 세균총과 같은 미생물학적 요인, 면역 매개에 의한 조직 손상과 같은 면역학적 요인 그리고 유전학적 요인 등이 복합적으로 발생기전에 관여 할 것이라고 추정한다. 특히 사이토카인과 같은 염증매개물질에 의해 세포매개염증반응의 일련의 과정이 유발 혹은 증폭되거나, 면역 조절 기능의 면화로 장 점막의 국소적 조직 손상을 유발하게 되며 면역 및 염증 반응이 적절하게 감소되지 않고 지속되어 만성 염증에 이르게 된다. 최근 이러한 염증반응에 중요한 역할을 담당하는 사이토카인 유전자에 관심이 몰리고 있다. 사이토카인은 활성화된 면역세포에서 주로 생성되는 당단백으로서 분자량이 8~10 kD 정도이며, 면역 반응시 T세포, B세포, 대식세포 등의 면역세포 상호간에 활성화, 증식 및 분화 등에 관계하여 국소적 조직 손상 및 염증반응을 일으킨다. 반면에 장의 구조와 기능에 있어 중요한 기질인 식이 섬유소에서 유래되는 Butyrate는 친염증성 사이토카인을 감소시키고 항염증성 사이토카인을 증가시킴으로써 장관 면역계에 대한 조절기능을 보이고 있다. 따라서 본 총설에서는 Butyrate의 항염증 효과에 대한 분자적 기작을 면역세포에서 Butyrate가 가지는 사이토카인 조절 능력을 통해 이해하고 Butyrate가 염증성 장질환에 대해 새로운 치료 전략을 제시 해 줄 것으로 기대한다. Inflammatory bowel disease, known as Crohn’s disease and ulcerative colitis, is an unexplained disease characterized by chronic inflammation that repeats a cycle of relapse, improvement, and complications. The cause of inflammatory bowel disease is not clearly known, but it is predicted that a complex of various factors precipitate its occurrence. In particular, inflammatory mediators, such as cytokine, induce an increase in cell-mediated inflammatory responses. Focal tissue damage then occurs in the intestinal mucosa because of the weakening of the immune-modulating functions of cotton. Immune and inflammatory responses do not decrease appropriately but continue until they lead to chronic inflammation. Current research has focused on the cytokine genes, which have important roles in these inflammatory responses. Cytokine is a glycoprotein that is produced mostly in activated immune cells. It connects the activation, multiplication, and differentiation between immune cells, which causes focal tissue damage and inflammatory response. Moreover, butyrate, which originates in dietary fiber and plays an important role in the structure and function of the intestinal area, shows control functions in the intestinal immune system by decreasing the proinflammatory cytokine and increasing the anti-inflammatory cytokine. Therefore, this research investigated the molecular mechanism of the anti-inflammatory effects of butyrate to comprehend the cytokine controlling abilities of butyrate in the immune cells. Butyrate is expected to have potential in new treatment strategies for inflammatory bowel disease.

Perfluorooctanoic acid alters T lymphocyte phenotypes and cytokine expression in mice

Son, Hee-Young,Lee, Soyoung,Tak, Eun-Nam,Cho, Hae-Sung,Shin, Hong-In,Kim, Sang-Hyun,Yang, Jae-Ho Wiley Subscription Services, Inc., A Wiley Company 2009 Environmental toxicology Vol.24 No.6

<P>Perfluorooctanoic acid (PFOA) has been used in commercial applications and detected in environmental matrices. This study focuses on whether PFOA affects the function of immune organs (spleen and thymus). Male ICR mice were exposed to 0, 2, 10, 50, and 250 ppm of PFOA in drinking water for 21 days. PFOA differently altered T lymphocyte populations. In the spleen, all doses of PFOA decreased CD8<SUP>+</SUP> lymphocytes; CD4<SUP>+</SUP> lymphocytes were increased by 50 and 250 ppm of PFOA. Exposure to 250 ppm of PFOA increased CD8<SUP>+</SUP> lymphocytes in the thymus. In the histopathological evaluation, the spleen of 250 ppm PFOA-treated groups revealed the increase of lymphoid hyperplasia of white pulp without significant alteration of red pulp. The thymus of 250 ppm PFOA-treated group showed decreased thickness of the cortex and medulla, but lymphoid cells were more densely arranged. PFOA elevated the expression of proinflammatory cytokines (tumor necrosis factor α, interleukin-1β, and interleukin-6) in the spleen, and proto-oncogene, c-myc, in the spleen and thymus. In conclusion, our data demonstrated that PFOA has an immunomodulatory effect by altering T lymphocyte phenotypes and gene expression of proinflammatory cytokines. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2009.</P>

Fisetin attenuates cerulein-induced acute pancreatitis through down regulation of JNK and NF-κB signaling pathways

Jo, I.J.,Bae, G.S.,Choi, S.B.,Kim, D.G.,Shin, J.Y.,Seo, S.H.,Choi, M.O.,Kim, T.H.,Song, H.J.,Park, S.J. North-Holland ; Elsevier Science Ltd 2014 european journal of pharmacology Vol.737 No.-

Acute pancreatitis (AP) is a complicated disease which is largely undiscovered. Fisetin, a natural flavonoid from fruits and vegetables, has been shown to have anti-inflammatory, antioxidant, and anti-cancer activities in various disease models. However, the effects of fisetin on AP have not been determined. Pre- and post- treatment of mice with fisetin reduced the severity of AP and pancreatitis-associated lung injury and inhibited several biochemical parameters (pancreatic weight to body weight ratio, amylase, lipase, and myeloperoxidase activity) and production of inflammatory cytokines. In pancreatic acinar cells, fisetin also inhibited cell death and production of inflammatory cytokines. In addition, fisetin inhibited activation of c-Jun NH<SUB>2</SUB>-terminal kinase (JNK) and nuclear factor (NF)-κB in vivo and in vitro. In conclusion, these results suggest that fisetin exhibits anti-inflammatory effect on AP and could be a beneficial agent in the treatment of AP and its pulmonary complications.

Ameliorative effects of curcumin and caffeic acid against short term exposure of waterpipe tobacco smoking on lung, heart and kidney in mice

Alia Khwaldeh,Ali Abu Siyam,Ahmed Alzbeede,Mohammad Farajallah,Ziad Shraideh,Darwish Badran 대한해부학회 2021 Anatomy & Cell Biology Vol.54 No.1

This study aims to evaluate the chemopreventive activity of two antioxidants (curcumin [CUM] and caffeic acid [CAF]), focusing on how these antioxidants could reduce cytotoxicity induced by short term secondhand exposure of waterpipe tobacco smoking. Forty-eight adult male BALB/c albino mice were equally divided into four groups. Antioxidants were delivered intraperitoneally, and the exposure to waterpipe smoking (WPS) was performed using a smoking machine. This experiment lasts for 14 consecutive days. Serum were collected from mice before dissection to quantify the activity of some liver enzymes, kidney function tests and proinflammatory cytokines. Lung, heart, and kidney were isolated and processed for light microscopy technique. Parallel treatment of CUM or CAF along with exposure to WPS showed less inflammation, less vacuolized, and more inflated alveoli, less deteriorations in cortex part of kidney, and less disintegration of cardiac myofibers in comparison to waterpipe only. Besides, CUM and CAF significantly reduced the activity of aspartate aminotransferase and proinflammatory cytokines. CUM and CAF were found to have anti-inflammatory and ameliorative effects against the cytotoxicity induced by exposure to waterpipe tobacco smoking, and CUM showed better chemopreventive activity than CAF.