Identification of novel cytokine biomarkers of hexanal exposure associated with pulmonary toxicity

Cho, Yoon,Song, Mi-Kyung,Kim, Tae Sung,Ryu, Jae-Chun Elsevier 2017 Environmental pollution Vol.229 No.-

<P><B>Abstract</B></P> <P>We aimed to investigate whether exposure to low-molecular-weight saturated aliphatic aldehydes induces an airway inflammation related to lung toxicity. In previous studies, we identified that several aldehydes induced inflammatory responses through the secretion of pro-inflammatory cytokines.</P> <P>Here, we elucidate on whether hexanal exposure induces the lung inflammatory response through the secretion of cytokines. Hexanal is one of the aldehydes, which are major components of indoor environmental irritants. Based on a multiplexed cytokine antibody array, we investigated the cytokine expression profiles to identify the significant biomarkers of hexanal exposure and to predict the possibility of adverse effects on pulmonary toxicity using <I>in vitro</I> and <I>in vivo</I> model systems. We identified the cytokines as biomarkers involved in LEPTIN, Interleukin(IL)-10, MCP-1, and VEGF that showed similar expression patterns in both <I>in vitro</I> and <I>in vivo</I> models under hexanal exposure. These cytokines are known to be associated with diverse lung diseases, such as lung fibrosis, chronic obstructive pulmonary disease (COPD), and non-small cell lung cancer.</P> <P>Although further studies are needed to identify the mechanisms that underlie hexanal pulmonary toxicity, these results provide the key cytokine biomarkers in response to hexanal exposure and indicate meaningful mechanistic previewing that can be indirectly attributed to lung disease.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Cytokine is important novel biomarkers in risk assessment. </LI> <LI> The cytokines LEPTIN, IL-10, MCP-1 and VEGF are important novel biomarker in hexanal exposure risk assessment. </LI> <LI> Hexanal is a well-known eye irritant and may cause respiratory irritation. </LI> <LI> It indicates the meaningful mechanistic previewing of hexanal-inflammatory lung disease. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Ochnaflavone의 면역보조제 효과

박민주(Minjoo Park),유기연(Ki Yon Rhew),한용문(Yongmoon Han) 대한약학회 2012 약학회지 Vol.56 No.6

In this present study, we determined whether or not there is an immunoadjuvant effect of ochnaflavone, a biflavone isolated from Lonicera japonica. As an antigenic source, the cell wall (CACW) of Candida albicans, a fungal pathogen, was used. CACW consists of 95% carbohydrate (mannan). In the experiments, BALB/c mice were immunized with emersion forms of CACW combined with or without ochnaflavone (Och) in the presence of IFA containing mineral oil or CACW alone. Then, the amounts of antisera collected from these mice groups were measured by the ELISA method. Data from these experiments showed that CACW combined with Och (CACW/Och/IFA) provoked the production of antisera app. 2.2 or 5 times more than the corresponding CACW/IFA or CACW alone (CACW/DPBS), respectively, in mice (P<0.05). We further examined the immune response type induced by Och. Analysis of the values of the IgG1/IgG2a ratios obtained from IgG isotyping revealed that Och induced Th2-immunity more dominantly than Th1. This finding was confirmed by cytokine profile. CACW/Och/IFA formulation induced IL-4 (Th2-type cytokine) more than IFNγ (Th1-type cytokine) as compared with CACW/IFA and CACW/DPBS formulations (P<0.05). All data combined, Och appears to have an immunoadjuvant activity that may convert Th1 immunity into Th2 immunity.

자궁내막증 환자의 말초혈액 및 복강액에서의 면역 세포 아형과 cytokine 농도의 특성

이제호(Je Ho Lee),김정구(Jung Gu Kim),최두석(Doo Seok Choi),이정원(Jeong Won Lee),윤병구(Byung Koo Yoon),양윤선(Yoon Sun Yang),김대원(Dae Won Kim),김동호(Dong Ho Kim) 대한산부인과학회 1998 Obstetrics & Gynecology Science Vol.41 No.12

N/A Objective: Endometriosis is a common and enigmatic disease affecting the reproductive life and health of women. Although the retrograde menstruation is a well established model for both transplantation and induction theories, the discrepancy between an incidence of retrograde menstruation and a prevalence for endometriosis suggests the possibility that the development and the progression of endometriosis is associated with individual susceptibility such as altered immune function. An impaired immune response may result in a defect in the ability to remove refluxed menstrual debris, thereby increasing the possibility of endometriosis. We carried out the study to elucidate the immunologic alteration in patients with endometriosis. Materials and Methods: Fifty-six patients undergoing pelviscopic surgery or open laparotomy for benign gynecological disease were enrolled in this study. The study groups consisted of group I (normal control patients, N=22), group II (endometriosis stage I and II, N 17), and group III (endometriosis stage III and IV, N=17). Lymphocyte subset including total T cell, helper T cell, suppressor T cell, B cell, helper/suppressor ratio, natural killer (NK) cell, monocyte population and cytokine profile including interleukin (lL)-1, soluble interleukin-2 receptor (slL-2R), IL-2, IL-6, IL-S, monocyte chemoattractant protein (MCP)-1 of peripheral blood and peritoneal fluid were analyzed using flow cytometry and enzyme-linked immunosorbant assay (ELISA) method respectively. Results: Peripheral blood and peritoneal fluid lymphocyte subset were indistinguishable among the 3 groups (p>0.05). And there were no significant difference in peripheral blood and peritoneal fluid cytokine profile among the 3 groups except peripheral blood MCP-1 level. Group III showed higher peripheral blood level of MCP-1 than control patients (p<0.05). Conclusion: In this study, lymphocyte subset and cytokine profile except MCP-1 in peripheral blood and peritoneal fluid from patients with endometriosis did not differ from those of the control group. Immunologic alterations of patients with endometriosis might be resulted not from the changes of the number of lymphocyte subsets and cytokine, but from the modification of functions.

육계에서 가시오갈피 급여에 따른 생산성, 혈액 생화학적 성상 및 면역 사이토카인 발현에 미치는 영향

장인석,문양수,손시환,Jang, In-Surk,Moon, Yang Soo,Sohn, Sea Hwan 한국가금학회 2015 韓國家禽學會誌 Vol.42 No.3

본 연구는 천연항산화 생리활성 소재로서 가시오갈피를 육계에게 0(CON), 0.5(AS1) 및 1.0%(AS2) 수준으로 급여하여 생산성, 면역장기 무게, 혈액 생화학적 성상 및 친염증 사이토카인 mRNA 발현에 미치는 영향을 조사하였다. 전 사육기간에서 가시오갈피 급여에 따른 체중, 증체 및 사료섭취량은 유의적 차이를 보이지 않았으나, AS2구에서 사료요구율이 유의적으로(p<0.05) 저하되었다. 면역장기 무게를 관찰한 결과, 간, 비장, F-낭 및 흉선 무게는 가시오갈피 급여에 따른 영향이 없었다. 혈액 생화학적 성분에서 albumin, total protein, cholesterol, AST, ALT 등과 같은 대부분의 성분은 대조구와 처리구간 차이는 없었다. 그러나 triglycerides는 대조구에 비해 AS2구에서 현저히(p<0.05) 높았고, glucose 수준은 대조구에 비해 가시오갈피 급여구에서 현저히(p<0.05) 증가되었다. 친염증 사이토카인 mRNA 발현을 조사한 결과, 가시오갈피 급여에 따라 백혈구의 IFN-${\gamma}$ mRNA 발현이 현저히(p<0.05) 감소되었으며, IL1-${\beta}$, IL-6, TNF-${\alpha}$, iNOS 등은 유의적 차이는 없었지만, 감소되는 경향이 있었다. 비장에서 친염증 사이토카인 발현은 유의적 차이가 없었다. 간 조직에서는 0.5% 가시오갈피 급여에 따라 iNOS mRNA 발현이 유의적으로(p<0.05) 감소하였지만, 다른 친염증 사이토카인 발현은 유의적 차이는 없었다. 따라서 육계 생산성 및 친염증 사이토카인 발현에 미치는 영향 등을 고려할 경우, 0.5% 수준의 가시오갈피 급여가 가장 바람직한 것으로 판단된다. This study was performed to examine the effects of dietary Acanthopanax senticosus (AS) on growth performance, immune organ weights, blood biochemical parameters and the expression of pro-inflammatory cytokines in broiler chicks. A total of 120 4-day-old birds were given a basal diet (CON) or a basal diet supplemented with 0.5% (AS1) or 1.0% (AS2) AS powder until the birds were 35 days of age. There was no difference in body weight, total gain, feed intake or immune organ weights among the treatment groups. However, the feed conversion ratio in the AS2 group was lower (p<0.05) than that in the CON group. Serum biochemical components, including AST (aspartate aminotransferase), ALT (alanine aminotransferase), albumin and total protein, were not affected by the dietary treatments, whereas glucose and triglyceride levels increased (p<0.05) in the AS2 group compared with the CON group. The AS1 group exhibited decreased mRNA expression (p<0.05) of IFN-${\gamma}$ in white blood cells and iNOS in the liver compared with the CON group. The other pro-inflammatory cytokines were unaffected by dietary AS supplementation, although there was a trend towards decreased expression of these genes, including those encoding Il-$1{\beta}$, IL-6 and TNF-${\alpha}$. In conclusion, dietary supplementation with 0.5% AS decreased the expression of several pro-inflammatory cytokines without affecting growth performance, suggesting that this supplement might be applicable as an immunoregulatory feed additive in broiler chicks.

Characterization of the cytokine profile of platelet rich plasma (PRP) and PRP-induced cell proliferation and migration: Upregulation of matrix metalloproteinase-1 and -9 in HaCaT cells

Hong-Bum Park,양정희,Kwang-Hoe Chung 대한혈액학회 2011 Blood Research Vol.46 No.4

Background :The underlying rationale of platelet rich plasma (PRP) therapy is that an injection of concentrated PRP at the site of injury may promote tissue repair via cytokine release from platelets. The molecular mechanisms of PRP therapy in the skin wound healing process are not well understood at present, and would benefit from clarification. Methods :PRP was stimulated with angonists for 5 min, and cytokine profile analysis was performed. To investigate the wound healing activity of PRP, cell proliferation and migration analyses were performed in skin cells. The effects of PRP were analyzed on the expression and activity of matrix metalloproteinase (MMP)-1, -2, -9, and the activation of transcription factors. Results :Thrombin was found to be a strong stimulator of PRP activation to release growth factors and chemokines. PRP induced cell proliferation and migration in HUVECs, HaCaT cells, and HDFs, as well as MMP-1and MMP-9 expression in HaCaT cells, but PRP did not have a significant effect on the expression or activity of MMPs in HDFs. The transcription factors, including signal transducer and activator of transcription-3 (STAT-3) were found to be phosphorylated following PRP treatment in HaCaT cells. Conclusion :In this study, we have identified the cytokine profile of activated PRP after agonist stimulation. We have shown that PRP plays an active role in promoting the proliferation and migration of skin cells via the regulation of MMPs, and this may be applicable to the future development of PRP therapeutics to enhance skin wound healing.

Myrtle Berries Seeds Prevent Dyslipidemia, Inflammation, and Excessive Cardiac Reactive Oxygen Species Production in Response to High-Fat Diet–Induced Obesity

Mohamed-Amine Jabri,Soumaya Hajaji,Ameni Omrani,Meriam Ben Youssef,Hichem Sebai 한국식품영양과학회 2023 Journal of medicinal food Vol.26 No.9

Anthocyanins are the major polyphenols in myrtle berries seeds aqueous extract (MBSAE). This studyinvestigates the protective potentials of MBSAE against obesity lipotoxicity and inflammation induced by a high-fat diet(HFD). It also describes the underlying mechanisms involved in its protective effects, with special attention to myocardialreactive oxygen species (ROS) production. Male Wistar rats were fed HFD for 6 weeks to induce obesity. MBSAE(100 mg/kg, b.w., p.o.) was orally administered to HFD-fed rats. Anti-obesity effects were triggered by the inhibitory action ofthe MBSAE against the weights of the body, its relative heart and the total abdominal fat. Treatment with MBSAE alsorestored the lipid profile to baseline compared with the HFD rats and lowered also the white blood cells count, includingneutrophils, lymphocytes, and basophils number as well as cytokines (tumor necrosis factor-a, interleukin [IL]-6, and IL-1b)levels in the rats serum, thus improving the tissue inflammatory status associated with obesity. Exposure of rats to HFD during6 weeks induces a myocardial oxidative stress as assessed by deleterious effects on lipoperoxidation state, antioxidant enzyme(SOD, CAT, and GPx) activities as well as sulfhydryl groups and GSH rates. Of importance, our study shows also that HFDprovokes a heart ROS (H2O2, OH, and O2-) overload. Of interest, all these oxidative heart disturbances were clearly endedby MBSAE treatment. Therefore, consumption of MBSAE as a natural extract may be a potential therapeutic strategy to treatobesity-associated diseases.

Adhesion of Lactic Acid Bacteria Can Modulate the Secretion of Cytokines on HT-29 Colon Adenocarcinoma Cells

( Jeong Min Lee ),( Kwon Tack Hwang ),( Kun Young Park ) 부산대학교 김치연구소 2005 김치의 과학과 기술 Vol.11 No.-

폐 편평세포암종 내 Leucine-Rich Repeat Kinase 2 암촉진 효과와 Interleukin-10 발현과의 연관성

Sung Won LEE,Sangwook PARK 대한임상검사과학회 2023 대한임상검사과학회지(KJCLS) Vol.55 No.2

Leucine-rich repeat kinase 2 (LRRK2)는 파킨슨병과 같은 신경퇴행성 질환의 병태생리학적인 측면에서 중요한 역할을하는 것으로 알려져 있고 주로 뇌뿐만 아니라 폐에서도 발현된다. 그러나 LRRK2 발현이 폐 편평세포암(lung squamous cell carcinoma, LUSC)과 같은 일반적인 폐암의 아형과 병인성이있는지는 불분명하다. 본 연구에서는 Kaplan Meier 플로터 생물정보학 온라인 도구를 사용하여 폐 편평세포암종 내에서LRRK2와의 예후 진단가치를 분석하였다. 폐 편평세포암종 환자는 LRRK2의 발현이 높아지면 더 나쁜 예후를 나타낸다고 알려져 왔다. LRRK2 발현이 높은 환자의 경우 종양 돌연변이 부담, 높은 신항원부하, 더 나쁜 생존율, 성별과 상관관계를 보였다. 더욱이, gene expression profiling interactive analysis 데이터분석에서 높은 LRRK2 발현을 가진 환자에서의 심각한증상은 항염증성 사이토카인(예, IL-4, IL-10 )의 높은 발현에 양의 상관관계를 보였지만 염증성 사이토카인은 상관성이 없었다. 이러한 결과에서 IL-10관련 유전자의 높은 발현은 더 나쁜 예후를 보이는 LRRK2-high 환자들에서 유의미하게 연관성을 보였다. 또한, tumor immunity estimation resource 데이터는큰포식세포가 LRRK2-high LUSC환자에서 IL-10의 기원세포중 하나임을 보여주었다. 본 연구를 통해 결과적으로 LRRK2-IL10 축의 가설이 LUSC 환자의 잠재적이 치료 표적과 예후 바이오 마커일 수 있음을 보여주었다.

가시오갈피 급여에 따른 육계의 혈액 생화학적 성상 및 친염증 사이토카인 mRNA 발현에 미치는 영향

송민혜,김하나,손시환,문양수,장인석 한국가금학회 2015 한국가금학회 정기총회 및 학술발표회 Vol.2015 No.11

Sputum Inflammatory Mediators Are Increased in Aspergillus fumigatus Culture-Positive Asthmatics

Michael A Ghebre,Dhananjay Desai,Amisha Singapuri,Joanne Woods,Laura Rapley,Suzanne Cohen,Athula Herath,Andrew J Wardlaw,Catherine H Pashley,Richard May,Chris E Brightling 대한천식알레르기학회 2017 Allergy, Asthma & Immunology Research Vol.9 No.2

Aspergillus fumigatus sensitization and culture in asthma are associated with disease severity and lung function impairment, but their relationship with airway inflammation is poorly understood. We investigated the profile of 24 sputum inflammatory mediators in A. fumigatus culture-positive or-negative moderate-to-severe asthmatics. Fifty-two subjects were recruited from a single center. A. fumigatus was cultured from 19 asthmatics. Asthma control, symptom score, lung function, and sputum cell count were not significantly different between the asthmatics with and without a positive A. fumigatus culture. All of the sputum mediators were numerically increased in subjects with a positive versus negative sputum A. fumigatus culture. Sputum TNF-R2 was significantly elevated (P=0.03) and the mediator that best distinguished A. fumigatus culture-positive from culturenegative subjects (receiver-operator characteristic area under the curve 0.66 [95% CI: 0.51 to 0.82, P=0.045]). A. fumigates-positive culture in moderate- to-severe asthma is associated with increased inflammatory sputum mediators.